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Artykuły w czasopismach na temat „Matrikines”

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Data publikacji: 15 marca 2025

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1

Papatheodoridi, M., P. Giuffrida, D. Canetti, Y. Yutaka, H. Hodgetts, A. Di Sabatino, H. Johnston i in. "P095 Newly discovered gut matrikines from Crohn’s disease intestinal tissue induce cell proliferation, activation and inflammatory response in intestinal myofibroblasts in vitro". Journal of Crohn's and Colitis 17, Supplement_1 (30.01.2023): i257—i260. http://dx.doi.org/10.1093/ecco-jcc/jjac190.0225.

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Abstract Background The interaction between intestinal myofibroblasts (iMFBs) and extracellular matrix (ECM) changes contributes to Crohn’s disease (CD) fibrosis, but the exact mechanisms are not yet clear. Our group recently discovered a selection of matrix-derived peptides (matrikines) that specifically appear in the intestinal tissue of patients with CD fibrostenosis.1 Here, we evaluate the in vitro effect of 19 matrikines (with various bioactivity likelihood) on primary human intestinal myofibroblasts (IMFBs), key cells in CD fibrosis. Methods Primary human iMFBS (500K/mL, Passage 4, Novabiosis) were cultured in serum-free medium (SFM) (DMEM high glucose, 1% sodium pyruvate, 1% non-essential aminoacids, 1% Antibiotics-Antimycotics and 3mg Gentamicin), complete medium (SFM with 10% fetal bovine serum), PDGF-bb 10ng/mL or treated with each of the matrikines at 10, 50, 100 μg/mL for 24hours. The effect of each matrikine on cell proliferation, gene expression and migration was assessed by BrdU, qPCR and Transwell assays, respectively. RNA sequencing data was analysed using the GSEA software. Results The effect on iMFBs proliferation and viability was tested with each of the 19 matrikines at 3 different doses (Table 1). Among 9 most likely-bioactive matrikines (M1-M9) (Figure 1), M1, M4, M7, M8 and M9 induced the highest effect in cell proliferation and were selected for further experiments. Gene expression assays showed upregulation of ACTA2 with M1 or M7 and upregulation of COL1A1 with M1, M7 or M8, indicating activation of the iMFBs (Figure 2). Transwell assays also showed that M1, M4 and M8 induce iMFB cell migration. A total of 1948, 1024, 460, 570, and 2749 differentially expressed genes (DEGs) were identified in iMBFs treated with M1, M4, M7, M8 and M9 vs no treatment, showing enrichment in pathways related to “smooth muscle contraction”, “fibroblast growth factor”, “cell migration”, “collagen formation”, “elastin formation” and “ECM organization”; most of which were also enriched by complete medium and/or PDGFbb that served as positive controls. However, pathways related to “proinflammatory and profibrotic mediators” or “vascular permeability” were only enriched in iMFBs treated with M1, M4, M8 and M9 or M1 and M9, respectively (Figure 3). Conclusion A selection of newly discovered CD-specific matrikines induce activation of iMFBs as well as inflammatory response and endothelial changes, suggesting an important role and therefore their potential value as biomarkers in the progression of intestinal fibrostenosis.
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2

Wells, J. Michael, Amit Gaggar i J. Edwin Blalock. "MMP generated matrikines". Matrix Biology 44-46 (maj 2015): 122–29. http://dx.doi.org/10.1016/j.matbio.2015.01.016.

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Burgess, Janette K., i Markus Weckmann. "Matrikines and the lungs". Pharmacology & Therapeutics 134, nr 3 (czerwiec 2012): 317–37. http://dx.doi.org/10.1016/j.pharmthera.2012.02.002.

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Mutgan, Ayse Ceren, Katharina Jandl i Grazyna Kwapiszewska. "Endothelial Basement Membrane Components and Their Products, Matrikines: Active Drivers of Pulmonary Hypertension?" Cells 9, nr 9 (3.09.2020): 2029. http://dx.doi.org/10.3390/cells9092029.

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Pulmonary arterial hypertension (PAH) is a vascular disease that is characterized by elevated pulmonary arterial pressure (PAP) due to progressive vascular remodeling. Extracellular matrix (ECM) deposition in pulmonary arteries (PA) is one of the key features of vascular remodeling. Emerging evidence indicates that the basement membrane (BM), a specialized cluster of ECM proteins underlying the endothelium, may be actively involved in the progression of vascular remodeling. The BM and its steady turnover are pivotal for maintaining appropriate vascular functions. However, the pathologically elevated turnover of BM components leads to an increased release of biologically active short fragments, which are called matrikines. Both BM components and their matrikines can interfere with pivotal biological processes, such as survival, proliferation, adhesion, and migration and thus may actively contribute to endothelial dysfunction. Therefore, in this review, we summarize the emerging role of the BM and its matrikines on the vascular endothelium and further discuss its implications on lung vascular remodeling in pulmonary hypertension.
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Patel, Dhiren F., i Robert J. Snelgrove. "The multifaceted roles of the matrikine Pro-Gly-Pro in pulmonary health and disease". European Respiratory Review 27, nr 148 (27.06.2018): 180017. http://dx.doi.org/10.1183/16000617.0017-2018.

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Matrikines are bioactive fragments of the extracellular matrix (ECM) that are fundamental in regulating a diverse array of physiological processes. The tripeptide Proline-Glycine-Proline (PGP) is a collagen-derived matrikine that has classically been described as a neutrophil chemoattractant. In this article, we describe our current understanding of the pathways that generate, degrade and modify PGP to dictate its bioavailability and stability. Additionally, we discuss our expanding appreciation of the capacity of PGP to regulate diverse cell types and biological processes, independent of its activity on neutrophils, including a putative role in wound repair. We argue that PGP functions as a primitive and conserved damage-associated molecular pattern, which is generated during infection or injury and subsequently acts to shape ensuing inflammatory and repair processes. As a fragment of the ECM that accumulates at the epicentre of the action, PGP is perfectly positioned to focus neutrophils to the exact site required and direct a localised repair response. However, it is essential that PGP is efficiently degraded, as if this matrikine is allowed to persist then pathology can ensue. Accordingly, we discuss how this pathway is subverted in chronic lung diseases giving rise to persistent inflammation and pathological tissue remodelling.
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6

Jariwala, Nathan, Matiss Ozols, Mike Bell, Eleanor Bradley, Andrew Gilmore, Laurent Debelle i Michael J. Sherratt. "Matrikines as mediators of tissue remodelling". Advanced Drug Delivery Reviews 185 (czerwiec 2022): 114240. http://dx.doi.org/10.1016/j.addr.2022.114240.

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Bellon, Georges, Laurent Martiny i Arnaud Robinet. "Matrix metalloproteinases and matrikines in angiogenesis". Critical Reviews in Oncology/Hematology 49, nr 3 (marzec 2004): 203–20. http://dx.doi.org/10.1016/j.critrevonc.2003.10.004.

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Sivaraman, K., i C. Shanthi. "Matrikines for therapeutic and biomedical applications". Life Sciences 214 (grudzień 2018): 22–33. http://dx.doi.org/10.1016/j.lfs.2018.10.056.

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Monboisse, Jean Claude, Karine Sénéchal, Jessica Thevenard, Laurent Ramont, Sylvie Brassart-Pasco i François-Xavier Maquart. "Matrikines : une nouvelle stratégie thérapeutique anti-cancéreuse". Biologie Aujourd'hui 206, nr 2 (2012): 111–23. http://dx.doi.org/10.1051/jbio/2012017.

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Schwanzer, Juliana. "Basement membrane-derived matrikines in pulmonary inflammation". Intrinsic Activity 12, Suppl.1 (16.09.2024): A1.2. http://dx.doi.org/10.25006/ia.12.s1-a1.2.

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Jariwala, Nathan, Matiss Ozols, Alexander Eckersley, Rachel Watson, Bezaleel Mambwe, Andrew Gilmore, Laurent Debelle i in. "P13 Prediction and in vitro characterization of tetrapeptide matrikines with diverse effects on human dermal fibroblasts". British Journal of Dermatology 189, nr 1 (lipiec 2023): e18-e19. http://dx.doi.org/10.1093/bjd/ljad174.034.

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Abstract The extracellular matrices (ECMs) of mammalian tissues play important roles in mediating and maintaining tissue function. However, aberrant and progressive remodelling of ECM components is a key feature in the pathology and ageing of many organs, including skin. Crucially, these degradative processes not only impair function, but may also release peptide fragments, known as matrikines, with cell signalling capabilities. In addition to endogenously produced matrikines, many exogenously applied bioactive peptides, with proven activity in skin, are homologous to naturally occurring amino acid sequences within ECM proteins. Despite the ability of some peptides to induce clinical benefits in aged skin, there has been no published conceptual framework to guide the prediction of new therapeutic matrikines. Here, we tested the hypothesis that small bioactive peptides (matrikines) can be predicted by the in silico digestion of dermal proteins by ECM proteases. We first identified a target cohort of 27 ECM proteins that were abundant in the dermis and/or were reported to undergo age-related remodelling. Utilizing an established machine-learning tool (PROSPER) we developed a PYTHON algorithm that could predict peptides liberated by in silico cleavage with eight skin-active enzymes [matrix metalloproteinase (MMP)-2, MMP-3, MMP-7 and MMP-9, cathepsin G and cathepsin K, granzyme B and elastase-2]. For the 27 target proteins this approach predicted the identity of 453 tetrapeptides. These peptides were predicted to be liberated predominantly from collagens (I, III, IV, VI and VII), some elastic fibre-associated proteins (EMILIN1 and fibulin-1) and the adhesive glycoprotein fibronectin. Eight peptides were selected for synthesis and biological activity testing based on their predicted protein sources, high solubility and likelihood of successful manufacture. The ability of these peptides to promote ECM synthesis (procollagen I, fibronectin, decorin, collagen IV, hyaluronic acid and fibrillin-1) in cultured human dermal fibroblasts (HDFs) was assessed by enzyme-linked immunosorbent assay or immunofluorescence (fibrillin-1 only). With the exception of hyaluronic acid, all of the peptides enhanced the synthesis of at least some ECM markers, including procollagen-I and decorin. Deposition of fibrillin-1, which is a sensitive marker of both skin ageing and repair, was significantly enhanced by three peptides. The ability of the peptides to influence the wider HDF secretome was assessed by liquid chromatography tandem mass spectrometry proteomics. Four of the peptides modulated synthesis of proteins in a wide range of functional classes, including enzyme inhibitors, ECM-affiliated proteins, cell adhesion molecules and basement membrane components, while the remaining four exhibited more targeted activities. We conclude that bioinformatic prediction of cleaved peptide fragments from ECM proteins can identify multiple small peptides with potentially beneficial activities for skin. This approach can both identify new matrikines and provide insights into the mechanisms underpinning tissue repair. Funding sources: this study was funded by the No. 7 Beauty Company.
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Altay Benetti, Ayça, Tamara Tarbox i Camillo Benetti. "Current Insights into the Formulation and Delivery of Therapeutic and Cosmeceutical Agents for Aging Skin". Cosmetics 10, nr 2 (25.03.2023): 54. http://dx.doi.org/10.3390/cosmetics10020054.

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“Successful aging” counters the traditional idea of aging as a disease and is increasingly equated with minimizing age signs on the skin, face, and body. From this stems the interest in preventative aesthetic dermatology that might help with the healthy aging of skin, help treat or prevent certain cutaneous disorders, such as skin cancer, and help delay skin aging by combining local and systemic methods of therapy, instrumental devices, and invasive procedures. This review will discuss the main mechanisms of skin aging and the potential mechanisms of action for commercial products already on the market, highlighting the issues related to the permeation of the skin from different classes of compounds, the site of action, and the techniques employed to overcome aging. The purpose is to give an overall perspective on the main challenges in formulation development, especially nanoparticle formulations, which aims to defeat or slow down skin aging, and to highlight new market segments, such as matrikines and matrikine-like peptides. In conclusion, by applying enabling technologies such as those delivery systems outlined here, existing agents can be repurposed or fine-tuned, and traditional but unproven treatments can be optimized for efficacious dosing and safety.
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13

Hornebeck, W., i F. X. Maquart. "Rôle des matrikines dans la progression du mélanome". Annales Pharmaceutiques Françaises 64, nr 2 (luty 2006): 83–86. http://dx.doi.org/10.1016/s0003-4509(06)75299-3.

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Maquart, François-Xavier. "Les matrikines anti-tumorales : intérêt potentiel en cancérologie". Bulletin de l'Académie Nationale de Médecine 194, nr 3 (marzec 2010): 633–46. http://dx.doi.org/10.1016/s0001-4079(19)32305-2.

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15

Maquart, F. X., G. Bellon, S. Pasco i J. C. Monboisse. "Matrikines in the regulation of extracellular matrix degradation". Biochimie 87, nr 3-4 (marzec 2005): 353–60. http://dx.doi.org/10.1016/j.biochi.2004.10.006.

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Papadas, Athanasios, Garrett Arauz, Alexander Cicala, Joshua Wiesner i Fotis Asimakopoulos. "Versican and Versican-matrikines in Cancer Progression, Inflammation, and Immunity". Journal of Histochemistry & Cytochemistry 68, nr 12 (6.07.2020): 871–85. http://dx.doi.org/10.1369/0022155420937098.

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Versican is an extracellular matrix proteoglycan with key roles in multiple facets of cancer development, ranging from proliferative signaling, evasion of growth-suppressor pathways, regulation of cell death, promotion of neoangiogenesis, and tissue invasion and metastasis. Multiple lines of evidence implicate versican and its bioactive proteolytic fragments (matrikines) in the regulation of cancer inflammation and antitumor immune responses. The understanding of the dynamics of versican deposition/accumulation and its proteolytic turnover holds potential for the development of novel immune biomarkers as well as approaches to reset the immune thermostat of tumors, thus promoting efficacy of modern immunotherapies. This article summarizes work from several laboratories, including ours, on the role of this central matrix proteoglycan in tumor progression as well as tumor-immune cell cross-talk:
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17

Ricard-Blum, Sylvie, i Romain Salza. "Matricryptins and matrikines: biologically active fragments of the extracellular matrix". Experimental Dermatology 23, nr 7 (lipiec 2014): 457–63. http://dx.doi.org/10.1111/exd.12435.

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Monboisse, Jean Claude, Jean Baptiste Oudart, Laurent Ramont, Sylvie Brassart-Pasco i François Xavier Maquart. "Matrikines from basement membrane collagens: A new anti-cancer strategy". Biochimica et Biophysica Acta (BBA) - General Subjects 1840, nr 8 (sierpień 2014): 2589–98. http://dx.doi.org/10.1016/j.bbagen.2013.12.029.

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Tran, Kien T., Philina Lamb i Jau-Shyong Deng. "Matrikines and matricryptins: Implications for cutaneous cancers and skin repair". Journal of Dermatological Science 40, nr 1 (październik 2005): 11–20. http://dx.doi.org/10.1016/j.jdermsci.2005.05.001.

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Pasco, Sylvie, Laurent Ramont, François-Xavier Maquart i Jean Claude Monboisse. "Control of melanoma progression by various matrikines from basement membrane macromolecules". Critical Reviews in Oncology/Hematology 49, nr 3 (marzec 2004): 221–23. http://dx.doi.org/10.1016/j.critrevonc.2003.09.006.

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Mileshina, S. E., A. A. Nikolin i I. G. Kozlov. "Effect of collagen matrikines on the functional state of human leukocytes". Immunologiya 41, nr 4 (2020): 295–303. http://dx.doi.org/10.33029/0206-4952-2020-41-4-295-303.

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Popov, Aleksandr, Emma Kozlovskaya, Tatyana Rutckova, Olga Styshova, Vyacheslav Makhankov, Aleksey Vakhrushev, Dmitry Hushpulian, Irina Gazaryan, Oksana Son i Ludmila Tekutyeva. "Matrikines of Sea Cucumbers: Structure, Biological Activity and Mechanisms of Action". International Journal of Molecular Sciences 25, nr 22 (10.11.2024): 12068. http://dx.doi.org/10.3390/ijms252212068.

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Matrikines (MKs), the products of enzymatic fragmentation of various extracellular matrix (ECM) proteins, regulate cellular activity by interacting with specific receptors. MKs affect cell growth, proliferation, and migration, can induce apoptosis and autophagy, and are also effectively used in biomedicine and functional nutrition. Recently, there has been great interest in the structural features and biological activity of MKs from various sources. This review summarized and analyzed the results of modern research on MKs from sea cucumbers, primarily from trepang (MKT). Particular attention is paid to the analysis of the existing knowledge on the antioxidant, anti-inflammatory and adaptogenic activities of these MKs and the possible mechanisms of their protective action.
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Maquart, François-Xavier, Alain Siméon, Sylvie Pasco i Jean-Claude Monboisse. "Régulation de l’activité cellulaire par la matrice extracelulaire : le concept de matrikines". Journal de la Société de Biologie 193, nr 4-5 (1999): 423–28. http://dx.doi.org/10.1051/jbio/1999193040423.

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Maquart, François-Xavier, Sylvie Pasco, Laurent Ramont, William Hornebeck i Jean-Claude Monboisse. "An introduction to matrikines: extracellular matrix-derived peptides which regulate cell activity". Critical Reviews in Oncology/Hematology 49, nr 3 (marzec 2004): 199–202. http://dx.doi.org/10.1016/j.critrevonc.2003.06.007.

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Labat-Robert, Jacqueline. "Sites cryptiques et matrikines : Effets cellulaires des peptides de fibronectine et de laminine." Journal de la Société de Biologie 197, nr 1 (2003): 45–51. http://dx.doi.org/10.1051/jbio/2003197010045.

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Heinz, Andrea, Michael C. Jung, Laurent Duca, Wolfgang Sippl, Samuel Taddese, Christian Ihling, Anthony Rusciani i in. "Degradation of tropoelastin by matrix metalloproteinases - cleavage site specificities and release of matrikines". FEBS Journal 277, nr 8 (22.03.2010): 1939–56. http://dx.doi.org/10.1111/j.1742-4658.2010.07616.x.

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Jariwala, N., M. Ozols, A. Eckersley, R. E. Watson, B. Mambwe, A. Gilmore, L. Debelle i in. "LB1797 Novel tetra-peptide matrikines mediate dermal and epidermal metabolism in human skin". Journal of Investigative Dermatology 143, nr 9 (wrzesień 2023): B35. http://dx.doi.org/10.1016/j.jid.2023.06.182.

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El-Houni, Zeyad, Alexander Eckersley, Mike Bell, Eleanor Bradley, Victoria Newton, Michael Sherratt i Qing Jun Meng. "P12 Tetrapeptide matrikines synchronize circadian rhythms and promote proliferation in human skin cells". British Journal of Dermatology 189, nr 1 (lipiec 2023): e18-e18. http://dx.doi.org/10.1093/bjd/ljad174.033.

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Abstract Circadian rhythms are intrinsically generated 24 h rhythms that play a vital role in enabling the skin to adapt temporally to various external stimuli. These include ultraviolet radiation, physical trauma and water loss. At the molecular level, circadian clocks consist of various clock genes and proteins, including Per2/Cry1 and Bmal1/Clock, forming autoregulatory feedback loops. Although these rhythms are known to be impaired in ageing skin, there are limited therapeutic options to restore skin cell circadian function. As small peptides with homology to amino acid sequences found in extracellular matrix proteins (matrikines) can beneficially affect clinical and histological markers of skin ageing, in this study we characterized the ability of two novel tetrapeptides to influence the cellular circadian clocks of skin cells. HaCat keratinocytes transduced with a human Per2::luc promoter-driven reporter were used to monitor the effects of two synthetically generated peptides, GPKG and LSVD, on the cells’ intrinsic circadian clock. Following administration of these peptides at various concentrations (4–16 ppm), the oscillatory activity of the cells was amplified up to twofold vs. the vehicle control. LSVD was found to induce Per2::luc promoter activity significantly (P < 0.05). In addition to enhancing circadian rhythmicity, both peptides were assessed for their proliferative effect (by Incucyte imaging and MTT cell proliferation assays). At the higher concentrations tested, both GPKG and LSVD significantly increased proliferation in HaCat keratinocytes (P < 0.05). In conclusion, these peptides have been found to be highly effective in synchronizing the circadian clock in skin cells, leading to changes in their behaviour. This implies that these new peptides may have beneficial effects on skin cells, in part, by improving their circadian function. Given the findings of clock disruption in a number of diseases, as well as with age, identifying compounds that can reset the clock in skin cells is an important approach to developing treatments that can improve the functioning of cutaneous physiological processes that are under circadian control. Funding sources: this study was funded by the No. 7 Beauty Company.
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Popov, Aleksandr, Emma Kozlovskaya, Tatyana Rutckova, Olga Styshova, Aleksey Vakhrushev, Elena Kupera i Ludmila Tekutyeva. "Antitumor Properties of Matrikines of Different Origins: Prospects and Problems of Their Application". International Journal of Molecular Sciences 24, nr 11 (30.05.2023): 9502. http://dx.doi.org/10.3390/ijms24119502.

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Matrikines (MKs) can be a rich source of functional nutrition components and additional therapy, thereby contributing to human health care and reducing the risk of developing serious diseases, including cancer. Currently, functionally active MKs as products of enzymatic transformation by matrix metalloproteinases (MMPs) are used for various biomedical purposes. Due to the absence of toxic side effects, low species specificity, relatively small size, and presence of various targets at the cell membranes, MKs often exhibit antitumor properties and, therefore, are promising agents for antitumor combination therapy. This review summarizes and analyzes the current data on the antitumor activity of MKs of different origins, discusses the problems and prospects for their therapeutic use, and evaluates the experimental results of studying the antitumor properties of MKs from different echinoderm species generated with the help of a complex of proteolytic enzymes from red king crab Paralithodes camtschatica. Special attention is paid to the analysis of possible mechanisms of the antitumor action of various functionally active MKs, products of the enzymatic activity of various MMPs, and the existing problems for their use in antitumor therapy.
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Fox, Jay W., Alexandra Rucavado, Teresa Escalante, Junho Kim i José M. Gutiérrez. "160. Role of SVMPs, Matrikines and TLR4 in Snake Venom Induced Edema and Inflammation". Toxicon 60, nr 2 (sierpień 2012): 177. http://dx.doi.org/10.1016/j.toxicon.2012.04.161.

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Coquerel, Bérénice, Florent Poyer, Frédéric Torossian, Virginie Dulong, Georges Bellon, Isabelle Dubus, Annie Reber i Jean-Pierre Vannier. "Elastin-derived peptides: Matrikines critical for glioblastoma cell aggressiveness in a 3-D system". Glia 57, nr 16 (grudzień 2009): 1716–26. http://dx.doi.org/10.1002/glia.20884.

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Brassart, Bertrand, Jordan Da Silva, Mélissa Donet, Emeline Seurat, Frédéric Hague, Christine Terryn, Fréderic Velard i in. "Tumour cell blebbing and extracellular vesicle shedding: key role of matrikines and ribosomal protein SA". British Journal of Cancer 120, nr 4 (luty 2019): 453–65. http://dx.doi.org/10.1038/s41416-019-0382-0.

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Popova, Nadezhda V., i Manfred Jücker. "The Functional Role of Extracellular Matrix Proteins in Cancer". Cancers 14, nr 1 (4.01.2022): 238. http://dx.doi.org/10.3390/cancers14010238.

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The extracellular matrix (ECM) is highly dynamic as it is constantly deposited, remodeled and degraded to maintain tissue homeostasis. ECM is a major structural component of the tumor microenvironment, and cancer development and progression require its extensive reorganization. Cancerized ECM is biochemically different in its composition and is stiffer compared to normal ECM. The abnormal ECM affects cancer progression by directly promoting cell proliferation, survival, migration and differentiation. The restructured extracellular matrix and its degradation fragments (matrikines) also modulate the signaling cascades mediated by the interaction with cell-surface receptors, deregulate the stromal cell behavior and lead to emergence of an oncogenic microenvironment. Here, we summarize the current state of understanding how the composition and structure of ECM changes during cancer progression. We also describe the functional role of key proteins, especially tenascin C and fibronectin, and signaling molecules involved in the formation of the tumor microenvironment, as well as the signaling pathways that they activate in cancer cells.
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Hope, Chelsea, Philip B. Emmerich, Athanasios Papadas, Adam Pagenkopf, Kristina A. Matkowskyj, Dana R. Van De Hey, Susan N. Payne i in. "Versican-Derived Matrikines Regulate Batf3–Dendritic Cell Differentiation and Promote T Cell Infiltration in Colorectal Cancer". Journal of Immunology 199, nr 5 (28.07.2017): 1933–41. http://dx.doi.org/10.4049/jimmunol.1700529.

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Aldag, Caroline, Diana Nogueira Teixeira i Phillip S. Leventhal. "Skin rejuvenation using cosmetic products containing growth factors, cytokines, and matrikines: a review of the literature". Clinical, Cosmetic and Investigational Dermatology Volume 9 (listopad 2016): 411–19. http://dx.doi.org/10.2147/ccid.s116158.

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Papadas, Athanasios, Evan Flietner, Zachary Morrow, Joshua Wiesner, Alexander Cicala, Adam Pagenkopf, Chelsea L. Hope i in. "Versican Proteolytic Fragments (Matrikines) Regulate the Intratumoral Dendritic Cell Milieu In Vivo: Implications for in Situ Tumor Vaccination". Blood 134, Supplement_1 (13.11.2019): 1210. http://dx.doi.org/10.1182/blood-2019-131582.

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Regulated proteolysis of the tolerogenic matrix proteoglycan versican (VCAN) through the actions of ADAMTS-proteases, is associated with enhanced CD8+ infiltration in both hematopoietic and solid tumors. However, it is unclear whether the enhanced CD8+ infiltration results from proteolysis-mediated depletion of precursor VCAN at the tumor site or from generation of bioactive proteolytic fragments ("matrikines") (e.g., the 441-aa N-terminal fragment of V1-VCAN isoform, versikine). We have previously shown that versikine promotes Batf3-dendritic cell (DC) generation from FLT3L-mobilized bone marrow (BM) progenitors in vitro. However, the effects of versikine in DC homeostasis in the tumor microenvironment in vivo are unknown. To investigate the effects of versikine in DC homeostasis in vivo, we utilized the first Ras-driven myeloma (MM) model (VQ model- Rajagopalan et al., Blood 132:1006, 2018) as well as transplantable solid tumor models in both C57BL/6J (LLC lung carcinoma) and Balb/c (4T1 mammary carcinoma) backgrounds. Tumor cells were stably engineered to secrete HA-tagged versikine vs. empty-vector (EV) controls. EV-VQ or versikine-VQ myeloma cells were implanted intracardiacally into C57BL/6J syngeneic recipients and mice were monitored until they developed myeloma-related end-organ damage (hindlimb paralysis). Both groups of mice were paralyzed at similar rates. Intratumoral conventional DCs (CD138-CD45+, CD11chi,MHC IIhiLy6C-, CD64-) clustered into two populations: cDC1 (Batf3-DC: CD24hi,CD11blo), a subset with crucial activity in cross-priming anti-tumor CD8+ T cells, and cDC2 (CD24lo, CD11bhi). Versikine enhanced intratumoral Batf3-DC frequency/infiltration, while cDC2 levels were diminished in versikine-VQ BM (Figure 1A)(Batf3-DC: 48% in EV-VQ vs. 72% in versikine-VQ, p-value= 0.0246; cDC2: 52% in EV-VQ vs. 28% in versikine-VQ, p=0.0312). Monocytic-derived DC (Mo-DC: CD11chi, MHC IIhi, Ly6C+, CD64+) frequency remained unchanged. Versikine's effects were replicated in 2 solid tumor models. Versikine-expressing tumors were characterized by significantly enhanced Batf3-DC infiltration (Fig. 1A, p-value= 0.0079 for 4T1 model and <0.0001 for LLC model), whereas cDC2 numbers were diminished (p-value: 0.0079 and <0.0001 respectively). Adoptive transfer of CD45.2+ pre-DC (SIRPaint, FLIT3+, CD11c+, MHC II-, Celltrace+) in LLC-EV and LLC-versikine tumors in CD45.1+ recipients did not show any differences in 3-day differentiation potential of DC precursors, implicating other mechanisms to explain the steady-state imbalance in DC subset frequencies. To examine whether versikine's effects on the intratumoral DC milieu in vivo could be therapeutically harnessed, we compared responses to STING agonist therapy between versikine-expressing and EV tumors. LLC-EV-OVA and LLC-versikine-OVA (ovalbumin, a model antigen) -expressing tumors received therapeutic intratumoral injections of DMXAA, a murine STING agonist. Analysis of splenocytes 5 days later showed a significant increase in the frequency of OVA antigen-specific, CD8+ (MHCI:SIINFEKL tetramer+) splenocytes in LLC-versikine-bearing animals (Figure 1B). Interestingly, there was a marked increase in total central memory T splenocytes (TCM) (CD62LhiCD44hi) harvested from LLC-versikine tumor-bearing mice. We conclude that versikine influences the DC milieu in the tumor bed with promotion of intratumoral cross-presenting Batf3-DC and depletion of the cDC2 subset. Our findings highlight an unappreciated facet of immune regulation of the tumor microenvironment through matrix proteolytic fragments ("matrikines"). Whereas detection of native VCAN proteolysis on myeloma biopsies (see abstract by Dhakal et al.in this meeting) portends adverse outcomes likely due to the tolerogenic effects of accumulated precursor VCAN at the tumor site, therapeutic use of the isolated, purified fragments may promote tumor innate sensing and effector priming. VCAN-matrikines, through their effects on intratumoral Batf3-DC and antigen-specific CD8+ T cell infiltration, may potentiate in situ vaccination strategies across diverse hematopoietic and solid tumor types. Figure 1 Disclosures No relevant conflicts of interest to declare.
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Taddese, Samuel, Anthony S. Weiss, Günther Jahreis, Reinhard H. H. Neubert i Christian E. H. Schmelzer. "In vitro degradation of human tropoelastin by MMP-12 and the generation of matrikines from domain 24". Matrix Biology 28, nr 2 (marzec 2009): 84–91. http://dx.doi.org/10.1016/j.matbio.2008.12.002.

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Niland, Stephan, i Johannes A. Eble. "Hold on or Cut? Integrin- and MMP-Mediated Cell–Matrix Interactions in the Tumor Microenvironment". International Journal of Molecular Sciences 22, nr 1 (28.12.2020): 238. http://dx.doi.org/10.3390/ijms22010238.

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The tumor microenvironment (TME) has become the focus of interest in cancer research and treatment. It includes the extracellular matrix (ECM) and ECM-modifying enzymes that are secreted by cancer and neighboring cells. The ECM serves both to anchor the tumor cells embedded in it and as a means of communication between the various cellular and non-cellular components of the TME. The cells of the TME modify their surrounding cancer-characteristic ECM. This in turn provides feedback to them via cellular receptors, thereby regulating, together with cytokines and exosomes, differentiation processes as well as tumor progression and spread. Matrix remodeling is accomplished by altering the repertoire of ECM components and by biophysical changes in stiffness and tension caused by ECM-crosslinking and ECM-degrading enzymes, in particular matrix metalloproteinases (MMPs). These can degrade ECM barriers or, by partial proteolysis, release soluble ECM fragments called matrikines, which influence cells inside and outside the TME. This review examines the changes in the ECM of the TME and the interaction between cells and the ECM, with a particular focus on MMPs.
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Niland, Stephan, Andrea Ximena Riscanevo i Johannes Andreas Eble. "Matrix Metalloproteinases Shape the Tumor Microenvironment in Cancer Progression". International Journal of Molecular Sciences 23, nr 1 (23.12.2021): 146. http://dx.doi.org/10.3390/ijms23010146.

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Cancer progression with uncontrolled tumor growth, local invasion, and metastasis depends largely on the proteolytic activity of numerous matrix metalloproteinases (MMPs), which affect tissue integrity, immune cell recruitment, and tissue turnover by degrading extracellular matrix (ECM) components and by releasing matrikines, cell surface-bound cytokines, growth factors, or their receptors. Among the MMPs, MMP-14 is the driving force behind extracellular matrix and tissue destruction during cancer invasion and metastasis. MMP-14 also influences both intercellular as well as cell–matrix communication by regulating the activity of many plasma membrane-anchored and extracellular proteins. Cancer cells and other cells of the tumor stroma, embedded in a common extracellular matrix, interact with their matrix by means of various adhesive structures, of which particularly invadopodia are capable to remodel the matrix through spatially and temporally finely tuned proteolysis. As a deeper understanding of the underlying functional mechanisms is beneficial for the development of new prognostic and predictive markers and for targeted therapies, this review examined the current knowledge of the interplay of the various MMPs in the cancer context on the protein, subcellular, and cellular level with a focus on MMP14.
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Karousou, Evgenia, Arianna Parnigoni, Paola Moretto, Alberto Passi, Manuela Viola i Davide Vigetti. "Hyaluronan in the Cancer Cells Microenvironment". Cancers 15, nr 3 (28.01.2023): 798. http://dx.doi.org/10.3390/cancers15030798.

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The presence of the glycosaminoglycan hyaluronan in the extracellular matrix of tissues is the result of the cooperative synthesis of several resident cells, that is, macrophages and tumor and stromal cells. Any change in hyaluronan concentration or dimension leads to a modification in stiffness and cellular response through receptors on the plasma membrane. Hyaluronan has an effect on all cancer cell behaviors, such as evasion of apoptosis, limitless replicative potential, sustained angiogenesis, and metastasis. It is noteworthy that hyaluronan metabolism can be dramatically altered by growth factors and matrikines during inflammation, as well as by the metabolic homeostasis of cells. The regulation of HA deposition and its dimensions are pivotal for tumor progression and cancer patient prognosis. Nevertheless, because of all the factors involved, modulating hyaluronan metabolism could be tough. Several commercial drugs have already been described as potential or effective modulators; however, deeper investigations are needed to study their possible side effects. Moreover, other matrix molecules could be identified and targeted as upstream regulators of synthetic or degrading enzymes. Finally, co-cultures of cancer, fibroblasts, and immune cells could reveal potential new targets among secreted factors.
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41

Rahman, Saeed, Malvika Nagrath, Sasikumar Ponnusamy i Praveen Arany. "Nanoscale and Macroscale Scaffolds with Controlled-Release Polymeric Systems for Dental Craniomaxillofacial Tissue Engineering". Materials 11, nr 8 (20.08.2018): 1478. http://dx.doi.org/10.3390/ma11081478.

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Tremendous progress in stem cell biology has resulted in a major current focus on effective modalities to promote directed cellular behavior for clinical therapy. The fundamental principles of tissue engineering are aimed at providing soluble and insoluble biological cues to promote these directed biological responses. Better understanding of extracellular matrix functions is ensuring optimal adhesive substrates to promote cell mobility and a suitable physical niche to direct stem cell responses. Further, appreciation of the roles of matrix constituents as morphogen cues, termed matrikines or matricryptins, are also now being directly exploited in biomaterial design. These insoluble topological cues can be presented at both micro- and nanoscales with specific fabrication techniques. Progress in development and molecular biology has described key roles for a range of biological molecules, such as proteins, lipids, and nucleic acids, to serve as morphogens promoting directed behavior in stem cells. Controlled-release systems involving encapsulation of bioactive agents within polymeric carriers are enabling utilization of soluble cues. Using our efforts at dental craniofacial tissue engineering, this narrative review focuses on outlining specific biomaterial fabrication techniques, such as electrospinning, gas foaming, and 3D printing used in combination with polymeric nano- or microspheres. These avenues are providing unprecedented therapeutic opportunities for precision bioengineering for regenerative applications.
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42

Revert-Ros, Francisco, Ignacio Ventura, Jesús A. Prieto-Ruiz, José Miguel Hernández-Andreu i Fernando Revert. "The Versatility of Collagen in Pharmacology: Targeting Collagen, Targeting with Collagen". International Journal of Molecular Sciences 25, nr 12 (13.06.2024): 6523. http://dx.doi.org/10.3390/ijms25126523.

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Collagen, a versatile family of proteins with 28 members and 44 genes, is pivotal in maintaining tissue integrity and function. It plays a crucial role in physiological processes like wound healing, hemostasis, and pathological conditions such as fibrosis and cancer. Collagen is a target in these processes. Direct methods for collagen modulation include enzymatic breakdown and molecular binding approaches. For instance, Clostridium histolyticum collagenase is effective in treating localized fibrosis. Polypeptides like collagen-binding domains offer promising avenues for tumor-specific immunotherapy and drug delivery. Indirect targeting of collagen involves regulating cellular processes essential for its synthesis and maturation, such as translation regulation and microRNA activity. Enzymes involved in collagen modification, such as prolyl-hydroxylases or lysyl-oxidases, are also indirect therapeutic targets. From another perspective, collagen is also a natural source of drugs. Enzymatic degradation of collagen generates bioactive fragments known as matrikines and matricryptins, which exhibit diverse pharmacological activities. Overall, collagen-derived peptides present significant therapeutic potential beyond tissue repair, offering various strategies for treating fibrosis, cancer, and genetic disorders. Continued research into specific collagen targeting and the application of collagen and its derivatives may lead to the development of novel treatments for a range of pathological conditions.
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43

Khokhlenkova, N. V., A. V. Soloviova, O. V. Filiptsova, O. S. Kaliuzhnaia i N. V. Dvinskykh. "The current state and prospects of peptides use in cosmeceuticals". News of Pharmacy 108, nr 2 (27.11.2024): 10–17. http://dx.doi.org/10.24959/nphj.24.157.

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Aim. To analyze the range of peptides in cosmeceuticals. Materials and methods. The study materials were publications in scientific periodicals. The study used methods of content analysis, comparative, logical, analytical methods and generalization of information. Results. The analysis of scientific literature data has shown that bioactive peptides of various origins are widely used as active ingredients in cosmeceuticals. In 2022, the global market for the synthesis of cosmetic peptides was estimated in 195.3 million USD. The market is expanding due to the growing consumer demand for skin care and anti-ageing products. Consumers are shifting towards a holistic approach to beauty, appreciating products that not only provide instant results, but also support the skin’s natural processes. Peptides, with their various benefits, perfectly match this approach by promoting skin elasticity from the inside, providing a long-lasting positive result. Peptides can be used to address specific skin problems, such as hyperpigmentation, acne and inflammation. According to the mechanism of action, biologically active peptides are classified as carrier peptides, signal peptides, neurotransmitter inhibitor peptides and enzyme inhibitor peptides. Carrier peptides facilitate the transport of cofactors, such as copper and manganese, across the skin barrier. Both cofactors are essential for enzymatic reactions involved in preventing aging and wound healing. Copper tripeptide-1 and manganese tripeptide-1 are examples of carrier peptides that have been successfully used to reduce fine lines, wrinkles and hyperpigmentation associated with photoaging. Signal peptides or matrikines are derived from extracellular matrix proteins, such as collagen, elastin and fibronectin. Matrikines interact with specific receptors that stimulate the synthesis, repair and remodeling of the extracellular matrix. These peptides also regulate the activity of certain key enzymes involved in the aging process, such as collagenase, elastase, tyrosinase and hyaluronidase. Neurotransmitter inhibitor peptides are the latest cosmeceutical peptides. Similar to botulinum toxins, these peptides prevent the release of acetylcholine, a neurotransmitter responsible for muscle contraction. Inhibiting this process relaxes facial muscles, preventing the formation of fine lines and wrinkles. Neurotransmitter inhibitor peptides are a safer alternative to traditional botulinum toxin treatment with fewer potential side effects. Enzyme inhibitor peptides have become popular active ingredients in anti-ageing cosmetics. This class of peptides inhibits the activity of certain enzymes involved in various biochemical processes of the skin. Their application in cosmeceuticals is to control or inhibit those processes that cause skin damage, aging or loss of elasticity. Conclusions. The study of peptides for use in cosmeceuticals has opened new prospects in skin care and aesthetic medicine. Bioactive peptides of various origins – from plants, animals, marine organisms, and edible insects – exhibit a wide range of properties, including antiaging, antioxidant, anti-inflammatory, and antimicrobial effects. Peptides open new horizons in the creation of innovative cosmeceuticals, especially when combined with other active components, such as antioxidants or retinoids. Their safety, ability to biodegrade and spot impact make peptides an attractive ingredient for solving various dermatological problems without the side effects of more aggressive skin correction methods.
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Хавинсон, В. Х., Н. С. Линькова, А. С. Дятлова, Е. О. Гутоп i О. А. Орлова. "SHORT PEPTIDES: REGULATION OF SKIN FUNCTION DURING AGING". Успехи геронтологии, nr 1 (12.04.2020): 46–54. http://dx.doi.org/10.34922/ae.2020.33.1.005.

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Для поддержания функций кожи при старении применяют короткие пептиды, которые могут проникать через интактный роговой слой эпидермиса и оказывать влияние на клетки дермы. Короткие пептиды являются веществами, участвующими в естественных метаболических реакциях клеток, многие из них обладают геропротекторными свойствами. В обзоре рассмотрены основные группы пептидов-регуляторов функций фибробластов кожи: матрикины, карнозин, «коллагеновые» пептиды, аналоги факторов роста и цитокинов, дефенсины, иммунопротекторные пептиды и полифункциональные пептиды. Полифункциональные пептиды ( AcSDKP, KED, AEDG, AED ) обладают геропротекторными свойствами, замедляют апоптоз и стимулируют пролиферацию клеток кожи, повышают функциональную активность фибробластов кожи, нормализуют гомеостаз внеклеточного матрикса, являются антиоксидантами, иммунопротекторами, могут активировать микроциркуляцию в дерме. Пептидная регуляция функций кожи при старении является быстро развивающейся областью молекулярной геронтологии. Short peptides are applied for supporting skin function during ageing, because they can permeate the intact stratum corneum of the epidermis and affect the cells of the dermis. Short peptides are part of natural metabolism of cells and many of them have geroprotective properties. In the review we are considering the base sorts of peptides that are used for normalized skin fibroblasts function: matrikines, carnosine, collagen peptides, cytokine and growth factor analogs, defensins, immunoprotective peptides and polyfunctional peptides. Polyfunctional peptides ( AcSDKP, KED, AEDG, AED ) have geroprotective properties, slow apoptosis and stimulate skin cell proliferation, also increase functional activity of skin fibroblasts, normalize intracellular matrix hemostasis. Polyfunctional peptides are the antioxidants and immunoprotectors and can activate microcirculation in dermis. Peptide regulation of skin function during ageing are the fast-developing and prospective area in molecular gerontology.
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Haywood, Joel, Jianxun Qi, Chun-Chi Chen, Guangwen Lu, Yingxia Liu, Jinghua Yan, Yi Shi i George F. Gao. "Structural basis of collagen recognition by human osteoclast-associated receptor and design of osteoclastogenesis inhibitors". Proceedings of the National Academy of Sciences 113, nr 4 (7.01.2016): 1038–43. http://dx.doi.org/10.1073/pnas.1522572113.

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Human osteoclast-associated receptor (OSCAR) is an immunoglobulin (Ig)-like collagen receptor that is up-regulated on osteoclasts during osteoclastogenesis and is expressed in a range of myeloid cells. As a member of the leukocyte receptor complex family of proteins, OSCAR shares a high degree of sequence and structural homology with other collagen receptors of this family, including glycoprotein VI, leukocyte-associated Ig-like receptor-1, and leukocyte Ig-like receptor B4, but recognizes a unique collagen sequence. Here, we present the crystal structures of OSCAR in its free form and in complex with a triple-helical collagen-like peptide (CLP). These structures reveal that the CLP peptide binds only one of the two Ig-like domains, the membrane-proximal domain (domain 2) of OSCAR, with the middle and trailing chain burying a total of 661 Å2 of solvent-accessible collagen surface. This binding mode is facilitated by the unusual topography of the OSCAR protein, which displays an obtuse interdomain angle and a rotation of domain 2 relative to the membrane-distal domain 1. Moreover, the binding of the CLP to OSCAR appears to be mediated largely by tyrosine residues and conformational changes at a shallow Phe pocket. Furthermore, we investigated CLP peptides as inhibitors of osteoclastogenesis and found that a peptide length of 40 amino acids is required to ensure adequate inhibition of osteoclastogenesis in vitro. These findings provide valuable structural insights into the mode of collagen recognition by OSCAR and into the use of synthetic peptide matrikines for osteoclastogenesis inhibition.
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Joshi, Raghav, Edi Goihberg, Wenying Ren, Monika Pilichowska i Paul Mathew. "Proteolytic fragments of fibronectin function as matrikines driving the chemotactic affinity of prostate cancer cells to human bone marrow mesenchymal stromal cells via the α5β1 integrin". Cell Adhesion & Migration 11, nr 4 (11.08.2016): 305–15. http://dx.doi.org/10.1080/19336918.2016.1212139.

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Duca, Laurent, Nicolas Floquet, Alain J. P. Alix, Bernard Haye i Laurent Debelle. "Elastin as a matrikine". Critical Reviews in Oncology/Hematology 49, nr 3 (marzec 2004): 235–44. http://dx.doi.org/10.1016/j.critrevonc.2003.09.007.

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Yeagle, P. "Matrikine regulates endothelial leakage". Science 348, nr 6233 (23.04.2015): 408. http://dx.doi.org/10.1126/science.348.6233.408-p.

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Hahn, Cornelia S., David W. Scott, Xin Xu, Mojtaba Abdul Roda, Gregory A. Payne, J. Michael Wells, Liliana Viera i in. "The matrikine N-α-PGP couples extracellular matrix fragmentation to endothelial permeability". Science Advances 1, nr 3 (kwiecień 2015): e1500175. http://dx.doi.org/10.1126/sciadv.1500175.

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The compartmentalization and transport of proteins and solutes across the endothelium is a critical biologic function altered during inflammation and disease, leading to pathology in multiple disorders. The impact of tissue damage and subsequent extracellular matrix (ECM) fragmentation in regulating this process is unknown. We demonstrate that the collagen-derived matrikine acetylated proline-glycine-proline (N-α-PGP) serves as a critical regulator of endothelial permeability. N-α-PGP activates human endothelial cells via CXC-chemokine receptor 2 (CXCR2), triggering monolayer permeability through a discrete intracellular signaling pathway. In vivo, N-α-PGP induces local vascular leak after subcutaneous administration and pulmonary vascular permeability after systemic administration. Furthermore, neutralization of N-α-PGP attenuates lipopolysaccharide-induced lung leak. Finally, we demonstrate that plasma from patients with acute respiratory distress syndrome (ARDS) induces VE-cadherin phosphorylation in human endothelial cells, and this activation is attenuated by N-α-PGP blockade with a concomitant improvement in endothelial monolayer impedance. These results identify N-α-PGP as a novel ECM-derived matrikine regulating paracellular permeability during inflammatory disease and demonstrate the potential to target this ligand in various disorders characterized by excessive matrix turnover and vascular leak such as ARDS.
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50

Abdul Roda, Mojtaba, Amanda M. Fernstrand, Frank A. Redegeld, J. Edwin Blalock, Amit Gaggar i Gert Folkerts. "The matrikine PGP as a potential biomarker in COPD". American Journal of Physiology-Lung Cellular and Molecular Physiology 308, nr 11 (1.06.2015): L1095—L1101. http://dx.doi.org/10.1152/ajplung.00040.2015.

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The lack of a well-characterized biomarker for the diagnosis of chronic obstructive pulmonary disease (COPD) has increased interest toward finding one, because this would provide potential insight into disease pathogenesis and progression. Since persistent neutrophilia is an important hallmark in COPD Pro-Gly-Pro (PGP), an extracellular matrix-derived neutrophil chemoattractant, has been suggested to be a potential biomarker in COPD. The purpose of this review is to critically examine both biological and clinical data related to the role of PGP in COPD, with particular focus on its role as a clinical biomarker and potential therapeutic target in disease. The data provided in this review will offer insight into the potential use of PGP as end point for future clinical studies in COPD lung disease. Following PGP levels during disease might serve as a guide for the progression of lung disorders.
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