Journal articles: 'LPAR'

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Park, Hoyong, Sungmin Kim, Jeehae Rhee, Hyeon-Joong Kim, Jung-Soo Han, Seung-Yeol Nah, and ChiHye Chung. "Synaptic enhancement induced by gintonin via lysophosphatidic acid receptor activation in central synapses." Journal of Neurophysiology 113, no. 5 (March 1, 2015): 1493–500. http://dx.doi.org/10.1152/jn.00667.2014.

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Lysophosphatidic acid (LPA) is one of the well-characterized, ubiquitous phospholipid molecules. LPA exerts its effect by activating G protein-coupled receptors known as LPA receptors (LPARs). So far, LPAR signaling has been critically implicated during early development stages, including the regulation of synapse formation and the morphology of cortical and hippocampal neurons. In adult brains, LPARs seem to participate in cognitive as well as emotional learning and memory. Recent studies using LPAR1-deficient mice reported impaired performances in a number of behavioral tasks, including the hippocampus-dependent spatial memory and fear conditioning tests. Nevertheless, the effect of LPAR activation in the synaptic transmission of central synapses after the completion of embryonic development has not been investigated. In this study, we took advantage of a novel extracellular agonist for LPARs called gintonin to activate LPARs in adult brain systems. Gintonin, a recently identified active ingredient in ginseng, has been shown to activate LPARs and mobilize Ca2+ in an artificial cell system. We found that the activation of LPARs by application of gintonin acutely enhanced both excitatory and inhibitory transmission in central synapses, albeit through tentatively distinct mechanisms. Gintonin-mediated LPAR activation primarily resulted in synaptic enhancement and an increase in neuronal excitability in a phospholipase C-dependent manner. Our findings suggest that LPARs are able to directly potentiate synaptic transmission in central synapses when stimulated exogenously. Therefore, LPARs could serve as a useful target to modulate synaptic activity under pathological conditions, including neurodegenerative diseases.

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Headen, Karmel V., Afolabi O. Ogunleye, and David E. Williams. "A High-resolution Immunohistochemical Method for studying Receptor Expression on the Periodontal Ligament of Whole-mount Human Tooth Roots." International Journal of Experimental Dental Science 5, no. 2 (2016): 99–103. http://dx.doi.org/10.5005/jp-journals-10029-1134.

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ABSTRACT Aims Our laboratory has found that lysophosphatidic acid (LPA) and its cognate receptors [LPARs, (LPA1–6)] expressed by human gingival fibroblasts (GF) and periodontal ligament fibroblasts (PDLF) play key roles in oral fibroblast homeostasis and are implicated in the inflammation seen in periodontal disease. We have reported that PDLF express LPA1 and LPA3; however, information on the gross topographic distribution of LPARs in the periodontal ligament (PDL) was lacking, and therefore, we developed a simple method for in situ labeling of LPARs in the PDL of extracted teeth. Materials and methods Sectioning or grinding thin sections of demineralized or native teeth and periodontium have long been the standard methodologies used to assess biomarker distribution in the PDL; however, we modified traditional immunohistochemical labeling and used whole teeth with fixed, solvent permeabilized PDLs. Results LPA1 and LPA3 were specifically labeled in the PDL and could be visualized at both the macroand micro-levels. Conclusion This technique effectively labeled LPARs, and it can serve as a basis for the in situ visualization of other biomolecules expressed in the PDL. Clinical Significance The ability to observe PDL LPAR distribution at the macro-level complements the microscopic data, and it is useful for detecting and documenting molecular changes in the PDL/PDLF that were brought about by age, experimental treatments, or pathologies like periodontal disease. How to cite this article Cerutis DR, Headen KV, Ogunleye AO, Williams DE. A High-resolution Immunohistochemical Method for studying Receptor Expression on the Periodontal Ligament of Whole-mount Human Tooth Roots. Int J Experiment Dent Sci 2016;5(2):99-103.

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Balijepalli, Pravita, Ciera C. Sitton, and Kathryn E. Meier. "Lysophosphatidic Acid Signaling in Cancer Cells: What Makes LPA So Special?" Cells 10, no. 8 (August 11, 2021): 2059. http://dx.doi.org/10.3390/cells10082059.

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Lysophosphatidic acid (LPA) refers to a family of simple phospholipids that act as ligands for G protein-coupled receptors. While LPA exerts effects throughout the body in normal physiological circumstances, its pathological role in cancer is of great interest from a therapeutic viewpoint. The numerous LPA receptors (LPARs) are coupled to a variety of G proteins, and more than one LPAR is typically expressed on any given cell. While the individual receptors signal through conventional GPCR pathways, LPA is particularly efficacious in stimulating cancer cell proliferation and migration. This review addresses the mechanistic aspects underlying these pro-tumorigenic effects. We provide examples of LPA signaling responses in various types of cancers, with an emphasis on those where roles have been identified for specific LPARs. While providing an overview of LPAR signaling, these examples also reveal gaps in our knowledge regarding the mechanisms of LPA action at the receptor level. The current understanding of the LPAR structure and the roles of LPAR interactions with other receptors are discussed. Overall, LPARs provide insight into the potential molecular mechanisms that underlie the ability of individual GPCRs (or combinations of GPCRs) to elicit a unique spectrum of responses from their agonist ligands. Further knowledge of these mechanisms will inform drug discovery, since GPCRs are promising therapeutic targets for cancer.

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Lee, Jong, Donghee Kim, Yoon Oh, and Hee-Sook Jun. "Lysophosphatidic Acid Signaling in Diabetic Nephropathy." International Journal of Molecular Sciences 20, no. 11 (June 11, 2019): 2850. http://dx.doi.org/10.3390/ijms20112850.

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Lysophosphatidic acid (LPA) is a bioactive phospholipid present in most tissues and body fluids. LPA acts through specific LPA receptors (LPAR1 to LPAR6) coupled with G protein. LPA binds to receptors and activates multiple cellular signaling pathways, subsequently exerting various biological functions, such as cell proliferation, migration, and apoptosis. LPA also induces cell damage through complex overlapping pathways, including the generation of reactive oxygen species, inflammatory cytokines, and fibrosis. Several reports indicate that the LPA–LPAR axis plays an important role in various diseases, including kidney disease, lung fibrosis, and cancer. Diabetic nephropathy (DN) is one of the most common diabetic complications and the main risk factor for chronic kidney diseases, which mostly progress to end-stage renal disease. There is also growing evidence indicating that the LPA–LPAR axis also plays an important role in inducing pathological alterations of cell structure and function in the kidneys. In this review, we will discuss key mediators or signaling pathways activated by LPA and summarize recent research findings associated with DN.

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Okusa, Mark D., Hong Ye, Liping Huang, Laura Sigismund, Timothy Macdonald, and Kevin R. Lynch. "Selective blockade of lysophosphatidic acid LPA3 receptors reduces murine renal ischemia-reperfusion injury." American Journal of Physiology-Renal Physiology 285, no. 3 (September 2003): F565—F574. http://dx.doi.org/10.1152/ajprenal.00023.2003.

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Lysophosphatidic acid (LPA) released during ischemia has diverse physiological effects via its G protein-coupled receptors, LPA1, LPA2, and LPA3 (formerly Edg-2, -4, and -7). We tested the hypothesis that selective blockade of LPA receptors affords protection from renal ischemia-reperfusion (I/R) injury. By real-time PCR, LPA1-3 receptor mRNAs were expressed in mouse renal cortex, outer medulla, and inner medulla with the following rank order LPA3 = LPA2 > LPA1. In C57BL/6 mice whose kidneys were subjected to ischemia and reperfusion, treatment with a selective LPA3 agonist, oleoyl-methoxy phosphothionate (OMPT), enhanced injury. In contrast, a dual LPA1/LPA3-receptor antagonist, VPC-12249, reduced I/R injury, but this protective effect was lost when the antagonist was coadministered with OMPT. Interestingly, delaying administration of VPC-12249 until 30 min after the start of reperfusion did not alter its efficacy significantly. We conclude that VPC-12249 reduces renal I/R injury predominantly by LPA3 receptor blockade and could serve as a novel compound in the treatment of ischemia acute renal failure.

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Chen, Min, L. Nicole Towers, and Kathleen L. O'Connor. "LPA2 (EDG4) mediates Rho-dependent chemotaxis with lower efficacy than LPA1 (EDG2) in breast carcinoma cells." American Journal of Physiology-Cell Physiology 292, no. 5 (May 2007): C1927—C1933. http://dx.doi.org/10.1152/ajpcell.00400.2006.

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Lysophosphatidic acid (LPA) acts via binding to specific G protein-coupled receptors and has been implicated in the biology of breast cancer. Here, we characterize LPA receptor expression patterns in common established breast cancer cell lines and their contribution to breast cancer cell motility. By measuring expression of the LPA receptors LPA1, LPA2, and LPA3 with real-time quantitative PCR, we show that the breast cancer cell lines tested can be clustered into three main groups: cells that predominantly express LPA1 (BT-549, Hs578T, MDA-MB-157, MDA-MB-231, and T47D), cells that predominantly express LPA2 (BT-20, MCF-7, MDA-MB-453, and MDA-MB-468), and a third group that shows comparable expression level of these two receptors (MDA-MB-175 and MDA-MB-435). LPA3 expression was detected primarily in MDA-MB-157 cells. Using a Transwell chemotaxis assay to monitor dose response, we find that cells predominantly expressing LPA1 have a peak migration rate at 100 nM LPA that drops off dramatically at 1 μM LPA, whereas cells predominantly expressing LPA2 show the peak migration rate at 1 μM LPA, which remains high at 10 μM. Using BT-20 cells, LPA2-specific small interfering RNA, and C3 exotransferase, we demonstrate that LPA2 can mediate LPA-stimulated cell migration and activation of the small GTPase RhoA. Using LPA2 small interfering RNA, exogenous expression of LPA1, and treatment with Ki16425 LPA receptor antagonist in the BT-20 cells, we further find that LPA1 and LPA2 cooperate to promote LPA-stimulated chemotaxis. In summary, our results suggest that the expression of both LPA1 and LPA2 may contribute to chemotaxis and may permit cells to respond optimally to a wider range of LPA concentrations, thus revealing a new aspect of LPA signaling.

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Turgut, Ali, Emre Bilgin, Mert Filibeli, İbrahim Kuşak, Mert Kumbaracı, and Önder Kalenderer. "A New Reference to Evaluate Syndesmosis in Sagittal Plane Radiographs of the Ankle: The Lateral Posterior Ankle Ratio." Journal of the American Podiatric Medical Association 109, no. 6 (November 1, 2019): 426–30. http://dx.doi.org/10.7547/17-134.

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Background: Confirmation of anatomical reduction of ankle syndesmosis is mandatory because improper reduction leads to poor functional results. Coronal plane evaluation of syndesmosis is well described in the literature, but there is little information about sagittal plane evaluation. We sought to evaluate the relationship of fibula and tibia in the sagittal plane and create a new reference that can be applied easily and reliably. Methods: Lateral ankle radiographs of 337 individuals with no history of ankle fracture were evaluated. A line was drawn between the anterior and posterior cortices of the distal lateral tibia, and the length of this line was measured (line 1). The distance between the anterior and posterior cortices of the fibula on this line was measured, and the center of this second distance was identified and marked. The posterior half of the fibular width was divided by line 1 and was named the lateral posterior ankle ratio (LPAR). Statistical analysis was performed by side and sex. Results: Mean patient age was 38.6 years; mean LPAR was 0.48. There was a significant difference between men and women by age (P < .001) and LPAR (P = .01). There was no significant difference between right and left ankles by age (P = .63) and LPAR (P = .64). The LPAR was less than 0.40 in 6.8% of the radiographs, 0.40 to 0.50 in 57.9%, and greater than 0.50 to 0.60 in 32.9%. Conclusions: The LPAR should approximate 50% in normal lateral ankle images and, by extrapolation, after syndesmotic reduction.

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Stope, Matthias B., Robert Mandelkow, Daniela Brunnert, Martin Weiss, and Martin Burchardt. "Lysophosphatidic acid receptor isoforms expression in prostate cancer cells is differentially regulated by the CYP17A1 inhibitor abiraterone and depends on the androgen receptor." Advances in Modern Oncology Research 2, no. 1 (February 19, 2016): 57. http://dx.doi.org/10.18282/amor.v2.i1.83.

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<p>Prostate cancer (PC) treatment with steroid synthesis inhibitor, abiraterone acetate (AA) provides substantial survival advantages in advanced PC therapy. Owing to AA's anti-proliferative efficacy, even in the absence of androgen receptor (AR), the molecular mode of action is suspected to be a result of simultaneously targeted cellular factors. The present study demonstrated a differentially regulated expression of proliferative lysophosphatidic acid receptor (LPAR) isoforms in androgen receptor AR-positive LNCaP cells incubated with AA. Since LPAR regulation in AR-negative PC-3 cells is unaffected, it could be assumed that AA’s anticancer activity on LPAR expression depends on AR signaling cascades.</p>

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Contos, James J. A., Isao Ishii, Nobuyuki Fukushima, Marcy A. Kingsbury, Xiaoqin Ye, Shuji Kawamura, Joan Heller Brown, and Jerold Chun. "Characterization of lpa2 (Edg4) and lpa1/lpa2 (Edg2/Edg4) Lysophosphatidic Acid Receptor Knockout Mice: Signaling Deficits without Obvious Phenotypic Abnormality Attributable to lpa2." Molecular and Cellular Biology 22, no. 19 (October 1, 2002): 6921–29. http://dx.doi.org/10.1128/mcb.22.19.6921-6929.2002.

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ABSTRACT Lysophosphatidic acid (LPA), a bioactive lipid produced by several cell types including postmitotic neurons and activated platelets, is thought to be involved in various biological processes, including brain development. Three cognate G protein-coupled receptors encoded by lpa1 /lp A1/Edg-2/Gpcr26, lpa2 /lp A2/Edg-4, and lpa3 /lp A3/Edg-7 mediate the cellular effects of LPA. We have previously shown that deletion of lpa1 in mice results in craniofacial dysmorphism, semilethality due to defective suckling behavior, and generation of a small fraction of pups with frontal hematoma. To further investigate the role of these receptors and LPA signaling in the organism, we deleted lpa2 in mice. Homozygous knockout (lpa2 (−/−)) mice were born at the expected frequency and displayed no obvious phenotypic abnormalities. Intercrosses allowed generation of lpa1 (−/−) lpa2 (−/−) double knockout mice, which displayed no additional phenotypic abnormalities relative to lpa1 (−/−) mice except for an increased incidence of perinatal frontal hematoma. Histological analyses of lpa1 (−/−) lpa2 (−/−) embryonic cerebral cortices did not reveal obvious differences in the proliferating cell population. However, many LPA-induced responses, including phospholipase C activation, Ca2+ mobilization, adenylyl cyclase activation, proliferation, JNK activation, Akt activation, and stress fiber formation, were absent or severely reduced in embryonic fibroblasts derived from lpa1 (−/−) lpa2 (−/−) mice. Except for adenylyl cyclase activation [which was nearly abolished in lpa1 (−/−) fibroblasts], these responses were only partially affected in lpa1 (−/−) and lpa2 (−/−) fibroblasts. Thus, although LPA2 is not essential for normal mouse development, it does act redundantly with LPA1 to mediate most LPA responses in fibroblasts.

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Tucker, B. J., C. A. Mundy, and R. C. Blantz. "Can causality be determined from proximal tubular reabsorption and peritubular physical factors?" American Journal of Physiology-Renal Physiology 250, no. 1 (January 1, 1986): F169—F175. http://dx.doi.org/10.1152/ajprenal.1986.250.1.f169.

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Many studies in the literature have drawn conclusions regarding the mechanism of change in absolute proximal tubular reabsorption (APR) based on steady-state measurements of proximal reabsorptive rates and the peritubular capillary. The proximal reabsorptive rate, APR, is the product of the effective reabsorptive pressure (ERP) and the peritubular capillary reabsorptive coefficient (LpAR) (APR = ERP . LpAR). The ERP is defined by the net hydrostatic and oncotic pressure gradient acting across the capillary wall from interstitium to peritubular capillary flow. The relationship APR = ERP . LpAR is predefined, and steady-state measurements do not permit determination of causality because primary changes in any variable obligate a proportional change in a second variable. As an example of the difficulties in interpretation of this type of analysis, we have examined the APR and factors contributing to ERP and LpAR before and after the administration of benzolamide, a carbonic anhydrase inhibitor, to saline-expanded Munich-Wistar rats. Alterations in peritubular capillary fluid uptake cannot always be interpreted as casual mechanisms for changes in absolute fluid reabsorption but may result from primary alterations in epithelial transport.

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Iacovelli, L., L. Capobianco, GM D'Ancona, A. Picascia, and A. De Blasi. "Regulation of lysophosphatidic acid receptor-stimulated response by G-protein-coupled receptor kinase-2 and beta-arrestin1 in FRTL-5 rat thyroid cells." Journal of Endocrinology 174, no. 1 (July 1, 2002): 103–10. http://dx.doi.org/10.1677/joe.0.1740103.

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Lysophosphatidic acid (LPA) is a naturally occurring phospholipid that activates a variety of biological activities including cell proliferation. Three mammalian LPA receptor (LPAr) subtypes have been identified by molecular cloning, named lp(A1), lp(A2) and lp(A3), that are coupled to heterotrimeric G-proteins for signal transduction. The LPAr are endogenously expressed in the rat thyroid cell line FRTL-5 and we used the FRTL-5 cells permanently transfected to obtain moderate overexpression of G-protein-coupled receptor kinase-2 (GRK2) or beta-arrestin1 to study whether GRK2 and beta-arrestin1 desensitise LPAr-mediated signalling and regulate LPA-stimulated functional effects. Using RT-PCR we documented that lp(A1), lp(A2) and lp(A3) receptors are all expressed in FRTL-5 cells. We then analysed the signal transduction of the LPAr in FRTL-5 cells. Exposure to LPA did not stimulate inositol phosphate formation nor cAMP accumulation but reduced forskolin-stimulated cAMP. LPA was also able to stimulate MAP kinase activation and this effect was abolished by pertussis toxin pretreatment. These results suggest that LPAr are mainly coupled to a pertussis toxin-sensitive G-protein in FRTL-5 cells. In order to investigate whether GRKs and arrestins are involved in the regulation of LPAr-mediated signalling, we used the FRTL-5 cell line permanently transfected to overexpress GRK2 (named L5GRK2 cells) or beta-arrestin1 (L5betaarr1 cells). The ability of LPA to inhibit forskolin-stimulated cAMP accumulation was blunted in L5GRK2 and more markedly in L5betaarr1. The MAP kinase activation was also blunted in L5GRK2 and in L5betaarr1B cells. Exposure to 20 microM LPA increased the phosphorylation of extracellular signal-regulated kinases ERK1/2 by approximately 3-fold in L5pBJI cells (FRTL-5 cells transfected with the empty vector pBJI) while it induced a modest increase in L5betaarr1 and was ineffective in L5GRK2. We measured [3H]thymidine uptake in L5betaarr1B and in L5 GRK2 cells to test whether GRK2 and beta-arrestin1 could have a role in the regulation of LPAr-mediated cell proliferation. The mitogenic response induced by 35 microM LPA was substantially blunted in L5betaarr1 (-69+/-6%) and in L5GRK2 (-69.8+/-4.5%) cells as compared with L5pBJI. Our findings document that the receptor-mediated responses elicited by LPA are regulated by GRK2 and beta-arrestin1 in FRTL-5 cells and indicate that this mechanism is potentially important for the control of the LPA-stimulated proliferative response.

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Markiewicz, W., K. Kamińska, M. Bogacki, T. Maślanka, and J. Jaroszewski. "Participation of analogues of lysophosphatidic acid (LPA): oleoyl-sn-glycero-3-phosphate (L-α-LPA) and 1-oleoyl-2-O-methyl-rac-glycerophosphothionate (OMPT) in uterine smooth muscle contractility of the pregnant pigs." Polish Journal of Veterinary Sciences 15, no. 4 (December 1, 2012): 635–43. http://dx.doi.org/10.2478/v10181-012-0100-9.

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Abstract Recent studies show that a representative of phospholipids, namely lysophosphatidic acid (LPA) and its receptors (LPA1-3) play a significant role in the reproductive processes, i. a, in the modulation of the uterine contractility. The participation of LPA3 in the reproductive processes has been revealed in mice and has not been studied in gilts. Therefore, in the present study we investigated the role/action of LPA and its receptors LPA1, LPA2 and LPA3 on the contraction activity in the porcine uterus. The study was conducted on an experimental model in which the pig uterus consisted of the one whole uterine horn and a part of the second horn, both connected with the uterine corpus. Uterine strips consisting of the endometrium with the myometrium (ENDO/MYO) and myometrium (MYO) alone were collected on days 12-14 of the estrous cycle (control group; n = 5) or pregnancy (experimental group; n = 5). Two analogues of LPA at increasing doses were used: oleoyl-sn-glycero- 3-phosphate (L-α-LPA, a selective agonist of LPA1 and LPA2 receptors; 10-7 M; 10-6 M and 10-5 M) and 1-oleoyl-2-O-methyl-rac-glycerophosphothionate (OMPT, a selective agonist of LPA3 receptor; 68 nM; 136 nM and 680 nM). L-α-LPA caused an increase in the contraction tension, amplitude and frequency of ENDO/MYO from the uterine horn with the developing embryos. This effect was not observed in MYO in both groups examined. In the ENDO/MYO strips of the uterine horn with developing embryos, OMPT significantly increased the contraction tension at the highest dose (680 nM) and amplitude at all doses examined, while frequency of contractions was decreased at doses of 136 nM and 680 nM. In the MYO strips of the uterine horn with embryos a significant increase in the contraction tension and amplitude after the highest dose of OMPT was observed. The results obtained imply the important role of receptors LPA1 , LPA2 and LPA3 in the contraction activity of the porcine uterus during early pregnancy.

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Onallah, Hadil, Ben Davidson, and Reuven Reich. "Diverse Effects of Lysophosphatidic Acid Receptors on Ovarian Cancer Signaling Pathways." Journal of Oncology 2019 (September 17, 2019): 1–10. http://dx.doi.org/10.1155/2019/7547469.

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Lysophosphatidic acid (LPA) is a bioactive phospholipid with mitogenic and growth factor-like activities affecting cell invasion, cancer progression, and resistance. It is produced mainly by autotaxin and acts on six G-protein-coupled receptors, LPAR1-6. LPA has recently been implicated as a growth factor present in ascites of ovarian cancer patients. However, mitogenic pathways stimulated by LPA via its receptors may involve any novel, thus far uncharacterized, signaling pathway(s). Here we show that three LPA receptors are involved in tumor progression by activation of both the AKT and ERK signaling pathways. CRISPR-edited LPAR2 and LPAR3 knockouts have opposing effects on ERK activation, whereas LPAR6 is involved in the activation of AKT, affecting cell migration and invasion. Our study identifies specific molecular machinery triggered by LPA and its receptors that modulates tumor cells and can serve as therapeutic target in this malignancy.

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Cha, Yoon Jin, and Ja Seung Koo. "Expression of Autotaxin–Lysophosphatidate Signaling-Related Proteins in Breast Cancer with Adipose Stroma." International Journal of Molecular Sciences 20, no. 9 (April 29, 2019): 2102. http://dx.doi.org/10.3390/ijms20092102.

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This research aimed to evaluate the expression and clinical implication of autotaxin (ATX)-lysophosphatidate (LPA) signaling-related proteins in breast cancer with adipose stroma. To this end, a tissue microarray (TMA) was constructed from 137 breast cancer tissues with adipose stroma and 329 breast cancer tissues with non-adipose stroma (inflammatory stroma: n = 81, 24.6%; fibrous stroma: n = 246, 75.4%). Immunohistochemical staining for ATX-LPA signaling-related proteins (ATX, LPA1, LPA2, and LPA3) was performed on the TMA. The results showed that LPA2 in tumor cells and LPA3 in stromal cells were highly expressed in breast cancer with adipose stroma and breast cancer with adipose and inflammatory stroma, respectively. Stromal LPA1 positivity (p = 0.017) and stromal LPA3 positivity (p = 0.004) were higher in breast cancer with adipose stroma containing CD68-positive crown-like structures (CLS). Stromal ATX positivity (p = 0.010) and stromal LPA3 positivity (p = 0.009) were higher in breast cancer with adipose tissue containing CD163-positive CLS. In breast cancer with adipose stroma, the number of CD163-positive macrophages was greater with stromal ATX positivity (p = 0.003), and the number of CD68-positive and CD163-positive macrophages were greater in cases with stromal LPA3 positivity. In conclusion, ATX-LPA signaling-related proteins are highly expressed in breast cancer with adipose stroma, with associated macrophage infiltration.

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Yun, C. Chris, Hong Sun, Dongsheng Wang, Raluca Rusovici, Amanda Castleberry, Randy A. Hall, and Hyunsuk Shim. "LPA2 receptor mediates mitogenic signals in human colon cancer cells." American Journal of Physiology-Cell Physiology 289, no. 1 (July 2005): C2—C11. http://dx.doi.org/10.1152/ajpcell.00610.2004.

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Lysophosphatidic acid (LPA) is a mediator of multiple cellular responses. LPA mediates its effects predominantly through the G protein-coupled receptors LPA1, LPA2, and LPA3. In the present work, we studied LPA2-mediated signaling using human colon cancer cell lines, which predominantly express LPA2. LPA2 activated Akt and Erk1/2 in response to LPA. LPA mediated Akt activation was inhibited by pertussis toxin (PTX), whereas Erk1/2 activation was completely inhibited by a blocker of phospholipase Cβ, U-73122. LPA also induced interleukin-8 (IL-8) synthesis in the colon cancer cells by primarily activating LPA2 receptor. We also found that LPA2 interacts with Na+/H+ exchanger regulatory factor 2 (NHERF2). Activation of Akt and Erk1/2 was significantly attenuated by silencing of NHERF2 expression by RNA interference, suggesting a pivotal role of NHERF2 in LPA2-mediated signaling. We found that expression of LPA2 was elevated, whereas expression of LPA1 downregulated in several types of cancers, including ovarian and colon cancer. We conclude that LPA2 is the major LPA receptor in colon cancer cells and cellular signals by LPA2 are largely mediated through its ability to interact with NHERF2.

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Lin, Kuan-Hung, Jui-Chung Chiang, Ya-Hsuan Ho, Chao-Ling Yao, and Hsinyu Lee. "Lysophosphatidic Acid and Hematopoiesis: From Microenvironmental Effects to Intracellular Signaling." International Journal of Molecular Sciences 21, no. 6 (March 16, 2020): 2015. http://dx.doi.org/10.3390/ijms21062015.

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Vertebrate hematopoiesis is a complex physiological process that is tightly regulated by intracellular signaling and extracellular microenvironment. In recent decades, breakthroughs in lineage-tracing technologies and lipidomics have revealed the existence of numerous lipid molecules in hematopoietic microenvironment. Lysophosphatidic acid (LPA), a bioactive phospholipid molecule, is one of the identified lipids that participates in hematopoiesis. LPA exhibits various physiological functions through activation of G-protein-coupled receptors. The functions of these LPARs have been widely studied in stem cells, while the roles of LPARs in hematopoietic stem cells have rarely been examined. Nonetheless, mounting evidence supports the importance of the LPA-LPAR axis in hematopoiesis. In this article, we have reviewed regulation of hematopoiesis in general and focused on the microenvironmental and intracellular effects of the LPA in hematopoiesis. Discoveries in these areas may be beneficial to our understanding of blood-related disorders, especially in the context of prevention and therapy for anemia.

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Hao, Feng, Fuqiang Zhang, Daniel Dongwei Wu, Dong An, Jing Shi, Guohong Li, Xuemin Xu, and Mei-Zhen Cui. "Lysophosphatidic acid-induced vascular neointimal formation in mouse carotid arteries is mediated by the matricellular protein CCN1/Cyr61." American Journal of Physiology-Cell Physiology 311, no. 6 (December 1, 2016): C975—C984. http://dx.doi.org/10.1152/ajpcell.00227.2016.

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Vascular smooth muscle cell (SMC) migration is an essential step involved in neointimal formation in restenosis and atherosclerosis. Lysophosphatidic acid (LPA) is a bioactive component of oxidized low-density lipoprotein and is produced by activated platelets, implying that LPA influences vascular remodeling. Our previous study revealed that matricellular protein CCN1, a prominent extracellular matrix (ECM) protein, mediates LPA-induced SMC migration in vitro. Here we examined the role of CCN1 in LPA-induced neointimal formation. By using LPA infusion of carotid artery in a mouse model, we demonstrated that LPA highly induced CCN1 expression (approximately six- to sevenfold) in neointimal lesions. Downregulation of CCN1 expression with the specific CCN1 siRNA in carotid arteries blocked LPA-induced neointimal formation, indicating that CCN1 is essential in LPA-induced neointimal formation. We then used LPA receptor knockout (LPA1−/−, LPA2−/−, and LPA3−/−) mice to examine LPA receptor function in CCN1 expression in vivo and in LPA-induced neointimal formation. Our data reveal that LPA1 deficiency, but not LPA2 or LPA3 deficiency, prevents LPA-induced CCN1 expression in vivo in mouse carotid arteries. We also observed that LPA1 deficiency blunted LPA infusion-induced neointimal formation, indicating that LPA1 is the major mediator for LPA-induced vascular remodeling. Our in vivo model of LPA-induced neointimal formation established a key role of the ECM protein CCN1 in mediating LPA-induced neointimal formation. Our data support the notion that the LPA1-CCN1 axis may be the central control for SMC migration and vascular remodeling. CCN1 may serve as an important vascular disease marker and potential target for vascular therapeutic intervention.

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Lee, Zendra, Ching-Ting Cheng, Helen Zhang, Mark A. Subler, Jinhua Wu, Abir Mukherjee, Jolene J. Windle, Ching-Kang Chen, and Xianjun Fang. "Role of LPA4/p2y9/GPR23 in Negative Regulation of Cell Motility." Molecular Biology of the Cell 19, no. 12 (December 2008): 5435–45. http://dx.doi.org/10.1091/mbc.e08-03-0316.

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Lysophosphatidic acid (LPA) is a ligand of multiple G protein–coupled receptors. The LPA1–3receptors are members of the endothelial cell differentiation gene (Edg) family. LPA4/p2y9/GPR23, a member of the purinergic receptor family, and recently identified LPA5/GPR92 and p2y5 are structurally distant from the canonical Edg LPA receptors. Here we report targeted disruption of lpa4in mice. Although LPA4-deficient mice displayed no apparent abnormalities, LPA4-deficient mouse embryonic fibroblasts (MEFs) were hypersensitive to LPA-induced cell migration. Consistent with negative modulation of the phosphatidylinositol 3 kinase pathway by LPA4, LPA4deficiency potentiated Akt and Rac but decreased Rho activation induced by LPA. Reconstitution of LPA4converted LPA4-negative cells into a less motile phenotype. In support of the biological relevance of these observations, ectopic expression of LPA4strongly inhibited migration and invasion of human cancer cells. When coexpressed with LPA1in B103 neuroblastoma cells devoid of endogenous LPA receptors, LPA4attenuated LPA1-driven migration and invasion, indicating functional antagonism between the two subtypes of LPA receptors. These results provide genetic and biochemical evidence that LPA4is a suppressor of LPA-dependent cell migration and invasion in contrast to the motility-stimulating Edg LPA receptors.

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Nyssens, Lucas, Martin Rack, and Jean-Pierre Raskin. "Effective resistivity extraction of low-loss silicon substrates at millimeter-wave frequencies." International Journal of Microwave and Wireless Technologies 12, no. 7 (June 23, 2020): 615–28. http://dx.doi.org/10.1017/s175907872000077x.

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AbstractThe effective resistivity (ρeff) is a figure of merit commonly used to assess the radio-frequency performance of a substrate from the measurements of coplanar waveguide lines. For highly resistive substrates, such as the trap-rich (TR) substrate, the extracted ρeff decreases by several orders of magnitude at millimeter-wave frequencies. The explanation for this decay is twofold. First, the imaginary part of the characteristic impedance ${\rm \lpar \Im }\lpar Z_c\rpar \rpar$ is not well extracted, which leads to an incorrect separation of the total losses among the metal and substrate losses. Second, the original expression of ρeff does not include dielectric losses, which might become non-negligible at millimeter-wave frequencies. This paper solves both issues by presenting a new procedure to extract ρeff and the dielectric losses simultaneously, and by introducing a novel method to correct ${\rm \Im }\lpar {Z_c} \rpar$. Furthermore, it is shown that this extraction method enables the correct extraction of substrate parameters up to 220 GHz of TR and high-resistivity silicon substrates. Finally, the origin of the large extracted value of dielectric loss is discussed in the potential presence of surface roughness and surface wave radiation. Both phenomena are discounted thanks to measurements of an additional reflective structure and a standard impedance substrate.

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Eaves, Allen. "Stem cell heterogeneity (discussion)." Stem Cells 15, S2 (April 1997): 217–20. http://dx.doi.org/10.1002/stem.5530150829.

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Varshney, Prateek, Vivek Sajal, K. P. Singh, Ravindra Kumar, and Navneet K. Sharma. "Strong terahertz radiation generation by beating of extra-ordinary mode lasers in a rippled density magnetized plasma." Laser and Particle Beams 31, no. 2 (June 2013): 337–44. http://dx.doi.org/10.1017/s0263034613000062.

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AbstractA scheme of terahertz radiation generation is proposed by beating of two extra-ordinary lasers having frequencies and wave numbers$\lpar {\rm \omega}_1\comma \; \vec k_1 \rpar $and$\lpar {\rm \omega}_2\comma \; \vec k_2 \rpar $, respectively in a magnetized plasma. Terahertz wave is resonantly excited at frequency$\lpar {\rm \omega}_1 - {\rm \omega}_2 \rpar $and wave number (k1 − k2 + q) with a wave number mismatch factorqwhich is introduced by the periodicity of plasma density ripples. In this process, the lasers exert a beat ponderomotive force on plasma electrons and impart them an oscillatory velocity with both transverse and longitudinal components in the presence of transverse static magnetic field. The oscillatory velocity couples with density ripples and produces a nonlinear current that resonantly excites the terahertz radiation. Effects of periodicity of density ripples and applied magnetic field are analyzed for strong THz radiation generation. The terahertz radiation generation efficiency is found to be directly proportional to the square of density ripple amplitude and rises with the magnetic field strength. With the optimization of these parameters, the efficiency ~10−3is achieved in the present scheme. The frequency and power of generated THz radiation can be better tuned with the help of parameters like density ripple amplitude, periodicity and applied magnetic field strength in the present scheme.

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Guo, Rishu, Elizabeth A. Kasbohm, Puneeta Arora, Christopher J. Sample, Babak Baban, Neetu Sud, Perumal Sivashanmugam, Nader H. Moniri, and Yehia Daaka. "Expression and Function of Lysophosphatidic Acid LPA1 Receptor in Prostate Cancer Cells." Endocrinology 147, no. 10 (October 1, 2006): 4883–92. http://dx.doi.org/10.1210/en.2005-1635.

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The bioactive phospholipid lysophosphatidic acid (LPA) promotes cell proliferation, survival, and migration by acting on cognate G protein-coupled receptors named LPA1, LPA2, and LPA3. We profiled gene expression of LPA receptors in androgen-dependent and androgen-insensitive prostate cancer cells and found that LPA1 gene is differentially expressed in androgen-insensitive and LPA-responsive but not androgen-dependent and LPA-resistant cells. In human prostate specimens, expression of LPA1 gene was significantly higher in the cancer compared with the benign tissues. The androgen-dependent LNCaP cells do not express LPA1 and do not proliferate in response to LPA stimulation, implying LPA1 transduces cell growth signals. Accordingly, stable expression of LPA1 in LNCaP cells rendered them responsive to LPA-induced cell proliferation and decreased their doubling time in serum. Implantation of LNCaP-LPA1 cells resulted in increased rate of tumor growth in animals compared with those tumors that developed from the wild-type cells. Growth of LNCaP cells depends on androgen receptor activation, and we show that LPA1 transduces Gαi-dependent signals to promote nuclear localization of androgen receptor and cell proliferation. In addition, treatment with bicalutamide inhibited LPA-induced cell cycle progression and proliferation of LNCaP-LPA1 cells. These results suggest the possible utility of LPA1 as a drug target to interfere with progression of prostate cancer.

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Varshney, Prateek, Vivek Sajal, Sweta Baliyan, Navneet K. Sharma, Prashant K. Chauhan, and Ravindra Kumar. "Strong terahertz radiation generation by beating of two x-mode spatial triangular lasers in magnetized plasma." Laser and Particle Beams 33, no. 1 (December 15, 2014): 51–58. http://dx.doi.org/10.1017/s0263034614000640.

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AbstractResonant THz radiation generation is proposed by beating of two spatial-triangular laser pulses of different frequencies (ω1, ω2) and wave numbers $\lpar \vec k_1 \comma \; \vec k_2 \rpar $ in plasma having external static magnetic field. Laser pulses co-propagating perpendicular to a dc magnetic field exert a nonlinear ponderomotive force on plasma electrons, imparting them an oscillatory velocity with finite transverse and longitudinal components. Oscillatory plasma electrons couple with periodic density ripples n′ = nq0eiqz to produce a nonlinear current, i.e., responsible for resonantly driving terahertz radiation at $\lpar {\rm \omega} = {\rm \omega} _1 - {\rm \omega} _2 \comma \; \vec k = \vec k_1 - \vec k_2 + \vec q\rpar $. Effects of THz wave frequency, laser beam width, density ripples, and applied magnetic field are studied for the efficient THz radiation generation. The frequency and amplitude of THz radiation were observed to be better tuned by varying dc magnetic field strength and parameters of density ripples (amplitude and periodicity). An efficiency about 0.02 is achieved for laser intensity of 2 × 1015 W/cm2 in a plasma having density ripples about 30%, plasma frequency about 1 THz and magnetic field about 100 kG.

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Daus-Magbual, Arlene, Roderick Daus-Magbual, and Allyson Tintiangco-Cubales. "Pin@y Educational PARtnerships: Ethnic Studies Students, Teachers and Leaders as Scholar Activists." AAPI Nexus Journal: Policy, Practice, and Community 16, no. 1-2 (September 23, 2019): 220–44. http://dx.doi.org/10.36650/nexus16.1-2_220-244_daus-magbual2tintiango-cubales.

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Although Filipinas/os/xs was (and continues to be) one of the fastest-growing populations in the United States, especially in San Francisco Bay Area, when Pin@y Educational Partnerships (PEP) started in 2001, there were limited services, curriculum, and research on Filipinas/os/xs at both the college and K–12 levels (Tintiangco-Cubales, Daus-Magbual, and Daus-Magbual, 2010). This resource essay focuses on the PEP’s de- velopment of Participatory Action Research (PAR) projects that were built through the direct result of university-school-community partnerships. We cover three innovative research methods known as Youth Participatory Action Research (YPAR), Teacher Participatory Action Research (TPAR), and Leadership Participatory Action Research (LPAR). YPAR, TPAR, and LPAR are informed by critical pedagogy, critical inquiry, and community responsive pedagogy (Daus-Magbual and Tintiangco-Cubales, 2016; Freire, 1970; Tintiangco-Cubales et al., 2016). Building on this AAPI Nexus issue’s theme, this essay demonstrates engaged social justice research across the educational pipeline and the power of collaboration between universities, schools, and communities. Through PEP’s PAR projects, we offer ways that students, educators, and leaders can work together to- ward transformative change in schools and communities.

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Gallardo, Felipe S., Adriana Córdova-Casanova, and Enrique Brandan. "The linkage between inflammation and fibrosis in muscular dystrophies: The axis autotaxin–lysophosphatidic acid as a new therapeutic target?" Journal of Cell Communication and Signaling 15, no. 3 (March 10, 2021): 317–34. http://dx.doi.org/10.1007/s12079-021-00610-w.

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AbstractMuscular dystrophies (MDs) are a diverse group of severe disorders characterized by increased skeletal muscle feebleness. In many cases, respiratory and cardiac muscles are also compromised. Skeletal muscle inflammation and fibrosis are hallmarks of several skeletal muscle diseases, including MDs. Until now, several keys signaling pathways and factors that regulate inflammation and fibrosis have been identified. However, no curative treatments are available. Therefore, it is necessary to find new therapeutic targets to fight these diseases and improve muscle performance. Lysophosphatidic acid (LPA) is an active glycerophospholipid mainly synthesized by the secreted enzyme autotaxin (ATX), which activates six different G protein-coupled receptors named LPA1 to LPA6 (LPARs). In conjunction, they are part of the ATX/LPA/LPARs axis, involved in the inflammatory and fibrotic response in several organs-tissues. This review recapitulates the most relevant aspects of inflammation and fibrosis in MDs. It analyzes experimental evidence of the effects of the ATX/LPA/LPARs axis on inflammatory and fibrotic responses. Finally, we speculate about its potential role as a new therapeutic pharmacological target to treat these diseases.

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Boruszewska, Dorota, Ana Catarina Torres, Ilona Kowalczyk-Zieba, Patricia Diniz, Mariana Batista, Luis Lopes-da-Costa, and Izabela Woclawek-Potocka. "The Effect of Lysophosphatidic Acid duringIn VitroMaturation of Bovine Oocytes: Embryonic Development and mRNA Abundances of Genes Involved in Apoptosis and Oocyte Competence." Mediators of Inflammation 2014 (2014): 1–12. http://dx.doi.org/10.1155/2014/670670.

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In the present study we examined whether LPA can be synthesized and act duringin vitromaturation of bovine cumulus oocyte complexes (COCs). We found transcription of genes coding for enzymes of LPA synthesis pathway (ATXandPLA2) and of LPA receptors (LPAR 1–4) in bovine oocytes and cumulus cells, followingin vitromaturation. COCs were maturedin vitroin presence or absence of LPA (10−5 M) for 24 h. Supplementation of maturation medium with LPA increased mRNA abundance ofFSTandGDF9in oocytes and decreased mRNA abundance ofCTSsin cumulus cells. Additionally, oocytes stimulated with LPA had higher transcription levels ofBCL2and lower transcription levels ofBAXresulting in the significantly lowerBAX/BCL2ratio. Blastocyst rates on day 7 were similar in the control and the LPA-stimulated COCs. Our study demonstrates for the first time that bovine COCs are a potential source and target of LPA action. We postulate that LPA exerts an autocrine and/or paracrine signaling, through several LPARs, between the oocyte and cumulus cells. LPA supplementation of maturation medium improves COC quality, and although this was not translated into an enhancedin vitrodevelopment until the blastocyst stage, improved oocyte competence may be relevant for subsequentin vivosurvival.

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Dreno, Brigitte. "Roferon‐A (interferon alpha 2a) combined with tigason (etretinate) for treatment of cutaneous T cell lymphomas." Stem Cells 11, no. 4 (1993): 269–75. http://dx.doi.org/10.1002/stem.5530110403.

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Llona-Minguez, Sabin, Artin Ghassemian, and Thomas Helleday. "Lysophosphatidic acid receptor (LPAR) modulators: The current pharmacological toolbox." Progress in Lipid Research 58 (April 2015): 51–75. http://dx.doi.org/10.1016/j.plipres.2015.01.004.

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Kučeráková, M., S. Vratislav, L. Kalvoda, and Z. Trojanová. "Analysis of preferential orientation in zirconium samples deformed by uniaxial tension using neutron and X-ray diffraction." Powder Diffraction 30, S1 (February 12, 2015): S52—S55. http://dx.doi.org/10.1017/s0885715614001316.

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Two series of zirconium samples were investigated by neutron and X-ray diffraction. First series of the samples was deformed at room temperature (RT), whereas the second series was deformed at 300 °C. Both series were deformed on uniaxial tensile machine INSTRON 5882 from strain 0 to 30% (strain step was 5%). The neutronographic texture measurements were performed on the KSN-2 neutron diffractometer located at the research reactor LVR-15 in the Nuclear Research Institute, plc. Rez, Czech Republic. The X-ray measurements were performed at the theta/theta X'Pert PRO diffractometer with the Cr X-ray tube. Observed data were processed by the software packages GSAS and X'Pert Texture. Preferential orientation of the $\left({10\bar 10} \right)$ and $\left({11\bar 20} \right)$ plane poles is found to be parallel to the rolling direction for both tested deformation series. Poles of the $\lpar 10\bar 12\rpar $ and $\lpar 10\bar 13\rpar $ planes tend to be parallel to the normal direction (Tables II and III). Orientation of the basal poles is tilted by 45° from the normal direction toward the transverse direction. Sharpness of the resulting texture increases with extends of the applied deformation as well as with rise of the tensile test temperature from the RT level to 300 °C.

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Lin, Songbai, Sei-Jung Lee, Hyunsuk Shim, Jerold Chun, and C. Chris Yun. "The absence of LPA receptor 2 reduces the tumorigenesis by ApcMin mutation in the intestine." American Journal of Physiology-Gastrointestinal and Liver Physiology 299, no. 5 (November 2010): G1128—G1138. http://dx.doi.org/10.1152/ajpgi.00321.2010.

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Lysophosphatidic acid (LPA) is a lipid mediator that mediates several effects that promote cancer progress. The LPA receptor type 2 (LPA2) expression is often elevated in several types of cancers, including colorectal cancer (CRC). In this study, we investigated the role of LPA2 in the development of intestinal adenomas by comparing Apc Min/+ mice with Apc Min/+ /Lpar2 −/− mice. There were 50% fewer intestinal adenomas in Apc Min/+ /Lpar2 −/− mice than Apc Min/+ mice. Smaller-size adenomas (<1 mm) were found at higher frequencies in Apc Min/+ /Lpar2 −/− mice compared with Apc Min/+ mice at the two age groups examined. The expression level of LPA2 correlated with increased size of intestinal adenomas. Reduced tumor multiplicity and size in Apc Min/+ /Lpar2 −/− mice correlated with decreased proliferation of intestinal epithelial cells. Apc Min/+ /Lpar2 −/− mice showed an increased level of apoptosis, suggesting that LPA2-mediated signaling stimulates intestinal tumor development and progress by regulating both cell proliferation and survival. In addition, the expression levels of Krüpple-like factor 5 (KLF5), β-catenin, cyclin D1, c-Myc, and hypoxia-inducible factor-1α (HIF-1α) were significantly altered in Apc Min/+ /Lpar2 −/− mice compared with Apc Min/+ mice. In vitro studies using HCT116 cells showed that LPA induced cyclin D1, c-Myc, and HIF-1α expression, which was attenuated by knockdown of LPA2. In summary, intestinal tumor initiated by Apc mutations is altered by LPA2-mediated signaling, which regulates tumor growth and survival by altering multiple targets.

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Lin, Yu-Nung, Gilbert Audira, Nemi Malhotra, Nguyen Thi Ngoc Anh, Petrus Siregar, Jen-Her Lu, Hsinyu Lee, and Chung-Der Hsiao. "A Novel Function of the Lysophosphatidic Acid Receptor 3 (LPAR3) Gene in Zebrafish on Modulating Anxiety, Circadian Rhythm Locomotor Activity, and Short-Term Memory." International Journal of Molecular Sciences 21, no. 8 (April 18, 2020): 2837. http://dx.doi.org/10.3390/ijms21082837.

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Lysophosphatidic acid (LPA) is a small lysophospholipid molecule that activates multiple cellular functions through pathways with G-protein-coupled receptors. So far, six LPA receptors (LPAR1 to LPAR6) have been discovered and each one of them can connect to the downstream cell message-transmitting network. A previous study demonstrated that LPA receptors found in blood-producing stem cells can enhance erythropoietic processes through the activation of LPAR3. In the current study, newly discovered functions of LPAR3 were identified through extensive behavioral tests in lpar3 knockout (KO) zebrafish. It was found that the adult lpar3 KO zebrafish display an abnormal movement orientation and altered exploratory behavior compared to that of the control group in the three-dimensional locomotor and novel tank tests, respectively. Furthermore, consistent with those results, in the circadian rhythm locomotor activity test, the lpar3 KO zebrafish showed a lower level of angular velocity and average speed during the light cycles, indicating an hyperactivity-like behavior. In addition, the mutant fish also exhibited considerably higher locomotor activity during the dark cycle. Supporting those findings, this phenomenon was also displayed in the lpar3 KO zebrafish larvae. Furthermore, several important behavior alterations were also observed in the adult lpar3 KO fish, including a lower degree of aggression, less interest in conspecific social interaction, and looser shoal formation. However, there was no significant difference regarding the predator avoidance behavior between the mutant and the control fish. In addition, lpar3 KO zebrafish displayed memory deficiency in the passive avoidance test. These in vivo results support for the first time that the lpar3 gene plays a novel role in modulating behaviors of anxiety, aggression, social interaction, circadian rhythm locomotor activity, and memory retention in zebrafish.

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Baden, S. B., and S. R. Kohn. "Portable Parallel Programming of Numerical Problems Under the LPAR System." Journal of Parallel and Distributed Computing 27, no. 1 (May 1995): 38–55. http://dx.doi.org/10.1006/jpdc.1995.1070.

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Alcántara-Hernández, Rocío, Aurelio Hernández-Méndez, Gisselle A. Campos-Martínez, Aldo Meizoso-Huesca, and J. Adolfo García-Sáinz. "Phosphorylation and Internalization of Lysophosphatidic Acid Receptors LPA1, LPA2, and LPA3." PLOS ONE 10, no. 10 (October 16, 2015): e0140583. http://dx.doi.org/10.1371/journal.pone.0140583.

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Ueda, Hiroshi, Hiroyuki Neyama, and Yosuke Matsushita. "Lysophosphatidic Acid Receptor 1- and 3-Mediated Hyperalgesia and Hypoalgesia in Diabetic Neuropathic Pain Models in Mice." Cells 9, no. 8 (August 16, 2020): 1906. http://dx.doi.org/10.3390/cells9081906.

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Lysophosphatidic acid (LPA) signaling is known to play key roles in the initiation and maintenance of various chronic pain models. Here we examined whether LPA signaling is also involved in diabetes-induced abnormal pain behaviors. The high-fat diet (HFD) showing elevation of blood glucose levels and body weight caused thermal, mechanical hyperalgesia, hypersensitivity to 2000 or 250 Hz electrical-stimulation and hyposensitivity to 5 Hz stimulation to the paw in wild-type (WT) mice. These HFD-induced abnormal pain behaviors and body weight increase, but not elevated glucose levels were abolished in LPA1−/− and LPA3−/− mice. Repeated daily intrathecal (i.t.) treatments with LPA1/3 antagonist AM966 reversed these abnormal pain behaviors. Similar abnormal pain behaviors and their blockade by daily AM966 (i.t.) or twice daily Ki16425, another LPA1/3 antagonist was also observed in db/db mice which show high glucose levels and body weight. Furthermore, streptozotocin-induced similar abnormal pain behaviors, but not elevated glucose levels or body weight loss were abolished in LPA1−/− and LPA3−/− mice. These results suggest that LPA1 and LPA3 play key roles in the development of both type I and type II diabetic neuropathic pain.

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Chen, Shee-Uan, Hsinyu Lee, Daw-Yuan Chang, Chia-Hung Chou, Chih-Yuan Chang, Kuang-Han Chao, Chung-Wu Lin, and Yu-Shih Yang. "Lysophosphatidic Acid Mediates Interleukin-8 Expression in Human Endometrial Stromal Cells through Its Receptor and Nuclear Factor-κB-Dependent Pathway: A Possible Role in Angiogenesis of Endometrium and Placenta." Endocrinology 149, no. 11 (July 10, 2008): 5888–96. http://dx.doi.org/10.1210/en.2008-0314.

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Lysophosphatidic acid (LPA) is a pleiotropic phospholipid molecule involved in inflammation, angiogenesis, would healing, and cancer invasion. Whereas serum lysophospholipase D activity increases in women with pregnancy, the role of LPA in pregnancy remains unclear. We investigated the expression of LPA receptors and function of LPA in endometrial stromal cells. Histologically normal endometrium was obtained from surgical specimens of women undergoing hysterectomy for leiomyoma. First-trimester decidua was obtained from women receiving elective termination of pregnancy. We examined the expressions of LPA1, LPA2, and LPA3 receptors in endometrial stromal cells. The effects of LPA on the expression of vascular endothelial growth factor, IL-6, and IL-8 were examined. Signal pathways of LPA were delineated. Functions of secretory angiogenic factors were tested using human endometrial microvascular endothelial cells. Immunoreactivity and mRNA of LPA1 receptors were identified in endometrial stromal cells. LPA enhanced IL-8 expression in a dose- and time-dependent manner, whereas vascular endothelial growth factor or IL-6 expression was not affected by LPA treatment. Mechanistic dissection disclosed that LPA functioned via the Gi protein, MAPK/p38 and nuclear factor-κB pathway. LPA-induced IL-8 enhanced migration, permeability, capillary tube formation, and proliferation of human endometrial microvascular endothelial cells. Endometrial stromal cells express LPA1 receptors. Through the LPA1 receptor, LPA induces IL-8 expression via a nuclear factor-κB-dependent signal pathway. These results could suggest that LPA may play a role in angiogenesis of endometrium and placenta through induction of IL-8 in endometrial stromal cells during pregnancy.

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Zeigler, Zella R., Douglas Jones, Craig S. Rosenfeld, and Richard K. Shadduck. "Recombinant human erythropoietin (rhuepo) for treatment of myelodysplastic syndrome." Stem Cells 11, no. 1 (1993): 49–55. http://dx.doi.org/10.1002/stem.5530110109.

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Zon, Leonard I., and Nathan Bahary. "Use of the zebrafish (danio rerio) to define hematopoiesis." Stem Cells 16, S1 (May 1998): 67–78. http://dx.doi.org/10.1002/stem.5530160709.

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Bahary, Nathan, and Leonard I. Zon. "Use of the Zebrafish (Danio rerio) to Define Hematopoiesis." Stem Cells 16, no. 2 (March 1998): 89–98. http://dx.doi.org/10.1002/stem.160089.

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Setiawan, Veronica Wendy, Susan E.Hankinson, Graham A.Colditz, David J.Hunter, and Immaculata De Vivo. "Estrogen Receptor β lpar;ESR2) Polymorphisms and Endometrial Cancer (United States)." Cancer Causes & Control 15, no. 6 (August 2004): 627–33. http://dx.doi.org/10.1023/b:caco.0000036170.28502.5f.

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Gruber, Johann, Françoise Geisen, Roswitha Sgonc, Alexander Egle, Andreas Villunger, Guenther Boeck, Günther Konwalinka, and Richard Greil. "2′,2′‐Difluorodeoxycytidine (Gemcitabine) Induces Apoptosis in Myeloma Cell Lines Resistant to Steroids and 2‐Chlorodeoxyadenosine (2‐CdA)." Stem Cells 14, no. 3 (May 1996): 351–62. http://dx.doi.org/10.1002/stem.140351.

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Ogawa, Makio. "Blast cell colony assays and LTC‐IC assay (discussion)." Stem Cells 15, S2 (April 1997): 197–98. http://dx.doi.org/10.1002/stem.5530150825.

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Mathew, Stephen O., Krithi K. Rao, Jong R. Kim, Nowland D. Bambard, and Porunelloor A. Mathew. "Functional role of human NK cell receptor 2B4 (CD244) isoforms." European Journal of Immunology 39, no. 6 (June 2009): 1632–41. http://dx.doi.org/10.1002/eji.200838733.

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Park, Heeyoung, Ali Sadra, and Sung-Oh Huh. "Therapy for neuroblastoma using aptamer-miRNA/siRNA conjugates targeting the LPAR pathway." IBRO Reports 6 (September 2019): S425. http://dx.doi.org/10.1016/j.ibror.2019.07.1352.

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Geng, Hui, Rongpei Lan, Yaguang Liu, Wei Chen, Meng Wu, Pothana Saikumar, Joel M. Weinberg, and Manjeri A. Venkatachalam. "Proximal tubule LPA1 and LPA2 receptors use divergent signaling pathways to additively increase profibrotic cytokine secretion." American Journal of Physiology-Renal Physiology 320, no. 3 (March 1, 2021): F359—F374. http://dx.doi.org/10.1152/ajprenal.00494.2020.

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Lysophosphatidic acid (LPA) increases platelet-derived growth factor-B (PDGFB) and connective tissue growth factor (CTGF) production and secretion by proximal tubule (PT) cells through LPA2 receptor-Gqα-αvβ6-integrin-mediated activation of transforming growth factor-β1 (TGFB1). LPA2, β6-integrin, PDGFB, and CTGF increase in kidneys after ischemia-reperfusion injury (IRI), coinciding with fibrosis. The TGFB1 receptor antagonist SD-208 prevents increases of β6-integrin, TGFB1-SMAD signaling, and PDGFB/CTGF expression after IRI and ameliorates fibrosis (Geng H, Lan R, Singha PK, Gilchrist A, Weinreb PH, Violette SM, Weinberg JM, Saikumar P, Venkatachalam MA. Am J Pathol 181: 1236‐1249, 2012; Geng H, Lan R, Wang G, Siddiqi AR, Naski MC, Brooks AI, Barnes JL, Saikumar P, Weinberg JM, Venkatachalam MA. Am J Pathol 174: 1291‐1308, 2009). We report now that LPA1 receptor signaling through epidermal growth factor receptor (EGFR)-ERK1/2-activator protein-1 cooperates with LPA2-dependent TGFB1 signaling to additively increase PDGFB/CTGF production and secretion by PT cells. Conversely, inhibition of both pathways results in greater suppression of PDGFB/CTGF production and secretion and promotes greater PT cellular differentiation than inhibiting one pathway alone. Antagonism of the LPA-generating enzyme autotaxin suppressed signaling through both pathways. After IRI, kidneys showed not only more LPA2, nuclear SMAD2/3, and PDGFB/CTGF but also increased LPA1 and autotaxin proteins, together with enhanced EGFR/ERK1/2 activation. Remarkably, the TGFB1 receptor antagonist SD-208 prevented all of these abnormalities excepting increased LPA2. SD-208 inhibits only one arm of LPA signaling: LPA2-Gqα-αvβ6-integrin-dependent production of active TGFB1 and its receptor-bound downstream effects. Consequently, far-reaching protection by SD-208 against IRI-induced signaling alterations and tubule-interstitial pathology is not fully explained by our data. TGFB1-dependent feedforward modulation of LPA1 signaling is one possibility. SD-208 effects may also involve mitigation of injury caused by IRI-induced TGFB1 signaling in endothelial cells and monocytes. Our results have translational implications for using TGFB1 receptor antagonists, LPA1 and LPA2 inhibitors concurrently, and autotaxin inhibitors in acute kidney injury to prevent the development of chronic kidney disease.

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Rasko, John E. J., Elizabeth O'Flaherty, and C. Glenn Begley. "Mpl Ligand (MGDF) Alone and in Combination with Stem Cell Factor (SCF) Promotes Proliferation and Survival of Human Megakaryocyte, Erythroid and Granulocyte/Macrophage Progenitors." Stem Cells 15, no. 1 (January 1997): 33–42. http://dx.doi.org/10.1002/stem.150033.

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Raman, N., R. Jeyamurugan, B. Rajkapoor, and V. Magesh. "Metal‐based antitumor, cytotoxic and antimicrobial activity: pharmacological evaluation of Knoevenagel condensate β‐diketone Schiff base thiosemicarbazone Cu(II) and Zn(II) complexes." Applied Organometallic Chemistry 23, no. 7 (July 2009): 283–90. http://dx.doi.org/10.1002/aoc.1512.

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Hawley, Robert G., and Donna A. Sobieski. "Germline Stem Cells (The Origin of Teenage Mutant Ninja Turtles®?)." Stem Cells 20, no. 6 (November 2002): 478–81. http://dx.doi.org/10.1634/stemcells.20-6-478.

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Rose, Robert B. "High‐resolution HF time of arrival measurements (1981–1985)." Radio Science 23, no. 3 (May 1988): 257–64. http://dx.doi.org/10.1029/rs023i003p00257.

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Khoi, Pham Ngoc, Shinan Li, Ung Trong Thuan, Dhiraj Kumar Sah, Taek Won Kang, Thi Thinh Nguyen, Sen Lian, Yong Xia, and Young Do Jung. "Lysophosphatidic Acid Upregulates Recepteur D’origine Nantais Expression and Cell Invasion via Egr-1, AP-1, and NF-κB Signaling in Bladder Carcinoma Cells." International Journal of Molecular Sciences 21, no. 1 (January 1, 2020): 304. http://dx.doi.org/10.3390/ijms21010304.

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Abstract:

Muscle invasive bladder carcinoma is a highly malignant cancer with a high mortality rate, due to its tendency to metastasize. The tyrosine kinase recepteur d’origine nantais (RON) promotes bladder carcinoma metastasis. Lysophosphatidic acid (LPA) is a phospholipid derivative, which acts as a signaling molecule to activate three high affinity G-protein coupled receptors, LPA1, LPA2, and LPA3. This in turn leads to cell proliferation and contributes to oncogenesis. However, little is known about the effects of LPA on invasive bladder cancer (IBC). In this study, we discovered that LPA upregulated RON expression, which in turn promoted cell invasion in bladder cancer T24 cells. As expected, we found that the LPA receptor was essential for the LPA induced increase in RON expression. More interestingly, we discovered that LPA induced RON expression via the MAPK (ERK1/2, JNK1/2), Egr-1, AP-1, and NF-κB signaling axes. These results provide experimental evidence and novel insights regarding bladder malignancy metastasis, which could be helpful for developing new therapeutic strategies for IBC treatment.

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Wocławek-Potocka, Izabela, Paulina Rawińska, Ilona Kowalczyk-Zieba, Dorota Boruszewska, Emilia Sinderewicz, Tomasz Waśniewski, and Dariusz Jan Skarzynski. "Lysophosphatidic Acid (LPA) Signaling in Human and Ruminant Reproductive Tract." Mediators of Inflammation 2014 (2014): 1–14. http://dx.doi.org/10.1155/2014/649702.

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Lysophosphatidic acid (LPA) through activating its G protein-coupled receptors (LPAR 1–6) exerts diverse cellular effects that in turn influence several physiological processes including reproductive function of the female. Studies in various species of animals and also in humans have identified important roles for the receptor-mediated LPA signaling in multiple aspects of human and animal reproductive tract function. These aspects range from ovarian and uterine function, estrous cycle regulation, early embryo development, embryo implantation, decidualization to pregnancy maintenance and parturition. LPA signaling can also have pathological consequences, influencing aspects of endometriosis and reproductive tissue associated tumors. The review describes recent progress in LPA signaling research relevant to human and ruminant reproduction, pointing at the cow as a relevant model to study LPA influence on the human reproductive performance.

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Journal articles on the topic 'LPAR'

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