Academic literature on the topic 'Hemidesmosome'
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Journal articles on the topic "Hemidesmosome"
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Baker, S. E., S. B. Hopkinson, M. Fitchmun, et al. "Laminin-5 and hemidesmosomes: role of the alpha 3 chain subunit in hemidesmosome stability and assembly." Journal of Cell Science 109, no. 10 (1996): 2509–20. http://dx.doi.org/10.1242/jcs.109.10.2509.
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Hemidesmosomes are complex macromolecular structures which integrate elements of the extracellular matrix and the cytoskeleton of epithelial cells. To characterize cell-matrix interactions in the hemidesmosome, we have made use of 804G cells which possess the unusual ability to assemble hemidesmosomes in vitro. During the course of our studies, we have raised a set of monoclonal antibodies against rat laminin-5, the major structural element comprising 804G matrix. One of these, termed CM6, recognizes the 150 kDa alpha chain of rat laminin-5 and binds the globular (G) domain of intact laminin-5 molecules as determined by rotary shadowing. CM6 antibodies perturb formed hemidesmosomes in 804G cells. In particular, within 1 hour of incubation of 804G cells with CM6 antibodies, colocalization of laminin-5 and alpha 6 beta 4 integrin is lost and by 2 hours, staining generated by hemidesmosomal antibodies appears primarily cytoplasmic in the perinuclear zone. Ultrastructurally, CM6 antibodies first appear to induce detachment of hemidesmosomes from the underlying matrix. Next, portions of the basal cell surface invaginate to form vesicles whose cytoplasmic-facing surface is coated with hemidesmosomes still associated with keratin intermediate filaments. Anchoring filaments extend into the inside compartment of the vesicles. We have also studied the impact of CM6 antibodies on a model system in which the matrix of 804G cells induces de novo assembly of hemidesmosomes in human keratinocytes. This process involves the plasma membrane reorganization of the hemidesmosome associated integrin alpha 6 beta 4 as well as a redistribution of other hemidesmosome components such as the 230 kDa bullous pemphigoid antigen. Pretreatment of 804G matrix with CM6 antibodies blocks such plasma membrane reorganization of hemidesmosome components and inhibits hemidesmosome formation. Our studies indicate a crucial role for the G domain of the alpha chain of laminin-5 in both nucleation of hemidesmosome assembly as well as maintenance of hemidesmosome structural integrity.
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Riddelle, K. S., K. J. Green, and J. C. Jones. "Formation of hemidesmosomes in vitro by a transformed rat bladder cell line." Journal of Cell Biology 112, no. 1 (1991): 159–68. http://dx.doi.org/10.1083/jcb.112.1.159.
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Two hemidesmosomal plaque components of 230 and 180 kD have recently been characterized using autoantibodies in the serum samples of bullous pemphigoid (BP) patients (Klatte, D. H., M. A. Kurpakus, K. A. Grelling, and J. C. R. Jones. 1989, J. Cell Biol. 109:3377-3390). These BP autoantibodies generate the type of staining patterns that one would predict for formed hemidesmosomes, i.e., a punctate staining pattern towards the substratum; in less than 50% of various primary epithelial and transformed epidermal cell lines even when such cells are maintained in culture for prolonged periods. In contrast, affinity-purified human autoantibodies against the 230-kD hemidesmosomal plaque component generate intense immunofluorescence staining along the region of cell-substratum interaction in the rat bladder tumor cell line 804G maintained on uncoated glass cover-slips. This pattern is distinct from that observed in the 804G cells using an antibody preparation directed against vinculin, a component of adhesion plaques. Ultrastructural analyses of the 804G cells reveals that hemidesmosome-like structures occur along the basal surface of cells where they abut the substratum. These structures are present in 804G cells maintained in culture in reduced levels of Ca2+ and are recognized by autoantibodies directed against the 230-kD hemidesmosomal plaque component as determined by immunogold ultrastructural localization. To study hemidesmosome appearance in this cell line, 804G cells were trypsinized and then allowed to readhere to glass coverslips. In rounded, unattached 804G cells, hemidesmosome-like plaque structures occur along the cell surface. These structures are recognized by the 230-kD autoantibodies. At 1 h after plating, hemidesmosomes are observed along the substratum attached surface of cells. Protein synthesis is not required for the appearance of these hemidesmosomes. Within 4 h of plating, autoantibody staining and hemidesmosomes appear towards the cell periphery. Subsequently, the polypeptide recognized by the BP autoantibodies becomes concentrated in the perinuclear region, where there are numerous hemidesmosomes. We propose that the hemidesmosomes in 804G cells are involved in cell-substratum adhesion. We discuss possible mechanisms of assembly of hemidesmosomes in the 804G cells. Indeed, the 804G cells should prove an invaluable cell line for the biochemical and molecular dissection of hemidesmosome structure, function, and assembly.
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Stahl, S., S. Weitzman, and J. C. Jones. "The role of laminin-5 and its receptors in mammary epithelial cell branching morphogenesis." Journal of Cell Science 110, no. 1 (1997): 55–63. http://dx.doi.org/10.1242/jcs.110.1.55.
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In vivo, normal mammary epithelial cells utilize hemidesmosome attachment devices to adhere to stroma. However, analyses of a potential role for hemidesmosomes and their components in mammary epithelial tissue morphogenesis have never been attempted. MCF-10A cells are a spontaneously immortalized line derived from mammary epithelium and possess a number of characteristics of normal mammary epithelial cells including expression of hemidesmosomal associated proteins such as the two bullous pemphigoid antigens, alpha 6 beta 4 integrin and its ligand laminin-5. More importantly, MCF-10A cells readily assemble mature hemidesmosomes when plated onto uncoated substrates. When maintained on matrigel, like their normal breast epithelial cell counterparts, MCF-10A cells undergo a branching morphogenesis and assemble hemidesmosomes at sites of cell-matrigel interaction. Function blocking antibodies specific for human laminin-5 and the alpha subunits of its two known receptors (alpha 3 beta 1 and alpha 6 beta 4 integrin) not only inhibit hemidesmosome assembly by MCF-10A cells but also impede branching morphogenesis induced by matrigel. Our results imply that the hemidesmosome, in particular those subunits comprising its laminin-5/integrin ‘backbone’, play an important role in morphogenetic events. We discuss these results in light of recent evidence that hemidesmosomes are sites involved in signal transduction.
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Rezniczek, Günther A., José M. de Pereda, Siegfried Reipert та Gerhard Wiche. "Linking Integrin α6β4-based Cell Adhesion to the Intermediate Filament Cytoskeleton: Direct Interaction between the β4 Subunit and Plectin at Multiple Molecular Sites". Journal of Cell Biology 141, № 1 (1998): 209–25. http://dx.doi.org/10.1083/jcb.141.1.209.
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Recent studies with patients suffering from epidermolysis bullosa simplex associated with muscular dystrophy and the targeted gene disruption in mice suggested that plectin, a versatile cytoskeletal linker and intermediate filament-binding protein, may play an essential role in hemidesmosome integrity and stabilization. To define plectin's interactions with hemidesmosomal proteins on the molecular level, we studied its interaction with the uniquely long cytoplasmic tail domain of the β4 subunit of the basement membrane laminin receptor integrin α6β4 that has been implicated in connecting the transmembrane integrin complex with hemidesmosome-anchored cytokeratin filaments. In vitro binding and in vivo cotransfection assays, using recombinant mutant forms of both proteins, revealed their direct interaction via multiple molecular domains. Furthermore, we show in vitro self-interaction of integrin β4 cytoplasmic domains, as well as disruption of intermediate filament network arrays and dislocation of hemidesmosome-associated endogenous plectin upon ectopic overexpression of this domain in PtK2 and/or 804G cells. The close association of plectin molecules with hemidesmosomal structures and their apparent random orientation was indicated by gold immunoelectron microscopy using domain-specific antibodies. Our data support a model in which plectin stabilizes hemidesmosomes, via directly interlinking integrin β4 subunits and cytokeratin filaments.
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Kurpakus, M. A., V. Quaranta, and J. C. Jones. "Surface relocation of alpha 6 beta 4 integrins and assembly of hemidesmosomes in an in vitro model of wound healing." Journal of Cell Biology 115, no. 6 (1991): 1737–50. http://dx.doi.org/10.1083/jcb.115.6.1737.
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A transmembrane extracellular matrix receptor of the integrin family, alpha 6 beta 4, is a component of the hemidesmosome, an adhesion complex of importance in epithelial cell-connective tissue attachment (Stepp, M. A., S. Spurr-Michaud, A. Tisdale, J. Elwell, and I. K. Gipson. 1990. Proc. Natl. Acad. Sci. USA. 87:8970-8974; Jones, J. C. R., M. A. Kurpakus, H. M. Cooper, and V. Quaranta. 1991. Cell Regulation. 2:427-438). Cytosolic components of hemidesmosomes include bullous pemphigoid (BP) antigens while extracellular components include a 125-kD component of anchoring filaments (CAF) and collagen type VII-containing anchoring fibrils. We have monitored the incorporation of the alpha 6 beta 4 integrins into forming hemidesmosomes in an in vitro wound-healing explant model. In epithelial cells recently migrated from the edges of unwounded sites over bare connective tissue, alpha 6 beta 4 first appears along the entire cell surface. At this stage, these cells contain little or no cytosolic hemidesmosomal components, at least as detectable by immunofluorescence using BP autoantibodies, whereas they are already positive for laminin and CAF. At a later stage, as cells become positive for cytosolic hemidesmosome components such as BP antigens as well as collagen type VII, alpha 6 beta 4 becomes concentrated along the basal pole of the epithelial cell where it abuts the connective tissue of the explant. Polyclonal antibodies to beta 4 do not interfere with the migration of epithelial cells in the explant. However, they prevent assembly of hemidesmosomal complexes and inhibit expression of collagen type VII in cells that have migrated over wound areas. In addition, they induce disruption of established hemidesmosomes in nonmigrating cells of the unwounded area of the explant. Monoclonal antibodies to alpha 6 have a more dramatic effect, since they completely detach epithelial cells in the unwounded area of the explant. Antibodies to CAF also detach epithelial cells in unwounded areas, apparently by inducing separation between epithelium and connective tissue at the lamina lucida of the basement membrane zone. These results suggest a model whereby polarization of alpha 6 beta 4 to the basal surface of the cells, perhaps induced by a putative anchoring filament-associated ligand, triggers assembly of hemidesmosome plaques.
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Rabinovitz, Isaac, Lobsang Tsomo та Arthur M. Mercurio. "Protein Kinase C-α Phosphorylation of Specific Serines in the Connecting Segment of the β4 Integrin Regulates the Dynamics of Type II Hemidesmosomes". Molecular and Cellular Biology 24, № 10 (2004): 4351–60. http://dx.doi.org/10.1128/mcb.24.10.4351-4360.2004.
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ABSTRACT Although the regulation of hemidesmosome dynamics during processes such as epithelial migration, wound healing, and carcinoma invasion is important, the mechanisms involved are poorly understood. The integrin α6β4 is an essential component of the hemidesmosome and a target of such regulation. Epidermal growth factor (EGF) can induce hemidesmosome disassembly by a mechanism that involves serine phosphorylation of the β4 integrin subunit. Using a combination of biochemical and mutational analyses, we demonstrate that EGF induces the phosphorylation of three specific serine residues (S1356, S1360, and S1364) located within the connecting segment of the β4 subunit and that phosphorylation on these residues accounts for the bulk of β4 phosphorylation stimulated by EGF. Importantly, phosphorylation of these serines is critical for the ability of EGF to disrupt hemidesmosomes. Using COS-7 cells, which assemble hemidesmosomes type II upon exogenous expression of the α6β4 integrin, we observed that expression of a β4 construct containing Ser→Ala mutations of S1356, S1360, and S1364 reduced the ability of EGF to disrupt hemidesmosomes and that this effect appears to involve cooperation among these phosphorylation sites. Moreover, expression of Ser→Asp mutants that mimic constitutive phosphorylation reduced hemidesmosome formation. Protein kinase C-α (PKC-α) is the kinase responsible for phosphorylating at least two of these serines, based on in vitro kinase assays, peptide mapping, and mutational analysis. Together, these results highlight the importance of serine phosphorylation in regulating type II hemidesmosome disassembly, implicate a cluster of serine residues within the connecting segment of β4, and argue for a key role for PKC-α in regulating these structures.
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Riddelle, K. S., S. B. Hopkinson, and J. C. Jones. "Hemidesmosomes in the epithelial cell line 804G: their fate during wound closure, mitosis and drug induced reorganization of the cytoskeleton." Journal of Cell Science 103, no. 2 (1992): 475–90. http://dx.doi.org/10.1242/jcs.103.2.475.
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Recently, we identified a novel epithelial cell line, 804G, derived from rat bladder, which readily forms hemidesmosomes in vitro. One of the major structural components of the plaques of 804G cell hemidesmosomes is a 230 kDa antigen recognized by autoantibodies in the sera of patients with bullous pemphigoid (BP). An additional polypeptide of 180 kDa also localizes to the hemidesmosome plaque of 804G cells as determined by immunoelectron microscopy. Using confocal fluorescence/phase microscopy, we have employed both 230 kDa and 180 kDa antibody probes to monitor the fate of hemidesmosomes following closure of in vitro wounds, during mitosis, and following drug induced disruption of the cytoskeleton. The punctate cell-substratum associated staining generated by the hemidesmosomal antibodies in stationary unwounded 804G cell cultures is greatly diminished or even lost in cells which enter wound sites, presumably in response to enhanced cell motility. Few, if any hemidesmosomes are observed at the ultrastructural level in cells which have migrated into the wound area. However, as closure of the wound becomes complete, staining along the substratum attached surface of cells returns. During mitosis, there is no obvious loss of hemidesmosomal antigens along the basal surface of 804G cells, and formed hemidesmosomes can be observed in mitotic cells at the ultrastructural level. In 804G cells treated with colchicine, the typical subnuclear pattern of distribution of hemidesmosomal antigens is unaffected. In contrast, following treatment of 804G cells with cytochalasin D, hemidesmosomal antigens become concentrated at the cell periphery and no longer appear in the subnuclear region. Furthermore, formed hemidesmosomes are observed at the cell periphery of cytochalasin D-treated cells by electron microscopy. We suggest that hemidesmosomal plaques are mobile within the plasma membrane. We speculate that hemidesmosomal interactions with extracellular ligands are dynamic and we discuss a possible mechanism by which cytochalasin D induces reorganization of hemidesmosomes along the basal surface of 804G cells.
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Moch, Marcin, and Rudolf E. Leube. "Hemidesmosome-Related Keratin Filament Bundling and Nucleation." International Journal of Molecular Sciences 22, no. 4 (2021): 2130. http://dx.doi.org/10.3390/ijms22042130.
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The epithelial cytoskeleton encompasses actin filaments, microtubules, and keratin intermediate filaments. They are interconnected and attached to the extracellular matrix via focal adhesions and hemidesmosomes. To study their interplay, we inhibited actin and tubulin polymerization in the human keratinocyte cell line HaCaT by latrunculin B and nocodazole, respectively. Using immunocytochemistry and time-lapse imaging of living cells, we found that inhibition of actin and tubulin polymerization alone or in combination induced keratin network re-organization albeit differently in each situation. Keratin filament network retraction towards the nucleus and formation of bundled and radial keratin filaments was most pronounced in latrunculin-B treated cells but less in doubly-treated cells and not detectable in the presence of nocodazole alone. Hemidesmosomal keratin filament anchorage was maintained in each instance, whereas focal adhesions were disassembled in the absence of actin filaments. Simultaneous inhibition of actin and tubulin polymerization, therefore, allowed us to dissect hemidesmosome-specific functions for keratin network properties. These included not only anchorage of keratin filament bundles but also nucleation of keratin filaments, which was also observed in migrating cells. The findings highlight the fundamental role of hemidesmosomal adhesion for keratin network formation and organization independent of other cytoskeletal filaments pointing to a unique mechanobiological function.
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Spinardi, L., Y. L. Ren, R. Sanders, and F. G. Giancotti. "The beta 4 subunit cytoplasmic domain mediates the interaction of alpha 6 beta 4 integrin with the cytoskeleton of hemidesmosomes." Molecular Biology of the Cell 4, no. 9 (1993): 871–84. http://dx.doi.org/10.1091/mbc.4.9.871.
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The alpha 6 beta 4 integrin is structurally distinct from all the other known integrins because the cytoplasmic domain of beta 4 is unusually large and contains four type III fibronectin-like modules toward its C-terminus. To examine the function of the beta 4 cytoplasmic tail, we have expressed full-length and truncated human beta 4 cDNAs in rat bladder epithelial 804G cells, which form hemidesmosome-like adhesions in vitro. The cDNA encoded wild-type beta 4 subunit associated with endogenous alpha 6 and was recruited at the cell surface within hemidesmosome-like adhesions. A recombinant form of beta 4, lacking almost the entire cytoplasmic domain associated with alpha 6, reached the cell surface but remained diffusely distributed. A beta 4 molecule lacking almost the entire extracellular portion did not associate with alpha 6 but was correctly targeted to the hemidesmosome-like adhesions. Thus, the cytoplasmic portion of beta 4 contains sequences that are required and may be sufficient for the assembly of the alpha 6 beta 4 integrin into hemidesmosomes. To localize these sequences we examined the properties of additional mutant forms of beta 4. A truncated beta 4 subunit, lacking the most C-terminal pair of type III fibronectin homology domains, was incorporated into hemidesmosome-like adhesions, but another recombinant beta 4 molecule, lacking both pairs of type III fibronectin repeats, was not. Finally a recombinant beta 4 molecule, which was created by adjoining the region of the cytoplasmic domain including all type III repeats to the transmembrane segment, was efficiently recruited in hemidesmosome-like adhesions. Taken together these results suggest that the assembly of the alpha 6 beta 4 integrin into hemidesmosomes is mediated by a 303-amino acid region of beta 4 tail that comprises the first pair of type III fibronectin repeats and the segment between the second and third repeats. These data imply a function of a specific segment of the beta 4 cytoplasmic domain in interaction with cytoskeletal components of hemidesmosomes.
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Jones, J. C., M. A. Kurpakus, H. M. Cooper, and V. Quaranta. "A function for the integrin alpha 6 beta 4 in the hemidesmosome." Cell Regulation 2, no. 6 (1991): 427–38. http://dx.doi.org/10.1091/mbc.2.6.427.
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Many epithelial cells appear to use cell-substratum adhesion complexes known as hemidesmosomes as the main means of anchorage to the connective tissue. Initially recognized as distinctive electron-dense images, hemidesmosomes are still poorly understood at the biochemical level. The regulation and mode of their assembly, which is disrupted in certain blistering diseases and is critical to proper wound repair, also remains to be elucidated. The integrin alpha 6 beta 4 is expressed along the basal surface of various epithelial cells. We show here that this integrin localizes to hemidesmosomes as determined by immunoelectron microscopy using antibodies directed against both the extra- and intracytoplasmic domains of alpha 6 beta 4. This result, which agrees with a recent study, suggests a functional role for the alpha 6 beta 4 integrin in the hemidesmosomes. We therefore investigated such a potential role for this integrin using the cultured rat bladder carcinoma cell line 804G, which has the uncommon ability to form hemidesmosomes in vitro when maintained on uncoated glass substrates. By immunoprecipitation and immunofluorescence, we show that 804G cells express alpha 6 beta 4 along their basal surface in a punctate pattern that overlaps with the distribution of hemidesmosomal plaque antigens. However, this pattern is altered when cells are plated in the presence of an antiserum directed against alpha 6 beta 4. Furthermore, no hemidesmosomes are detectable at the ultrastructural level in the alpha 6 beta 4 antibody-treated cells compared with control cells. These results indicate that integrins may play a critical role in assembly and adhesive functions of the hemidesmosome.
Dissertations / Theses on the topic "Hemidesmosome"
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Koster, Jan Johannes Bernardus. "Plakin interactions in the hemidesmosome." [S.l. : Amsterdam : s.n.] ; Universiteit van Amsterdam [Host], 2003. http://dare.uva.nl/document/69999.
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Leivo, T. (Tomi). "Basement membrane zone proteins, epithelial integrins and TGF-β system in reepithelialization, dermatitis herpetiformis and psoriasis:modulation by isotretinoin, betamethasone and calcipotriol". Doctoral thesis, University of Oulu, 2000. http://urn.fi/urn:isbn:951425712X.
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Abstract
TGF-βs are cytokines that signal through the receptor
complex of type I and type II receptors. Hemidesmosome (BP180, BP230,
plectin/HD1, α6β4 integrin), anchoring
filaments (laminin 5), and anchoring fibrils (collagen VII) form
a hemidesmosomal adhesion complex that provides stable adherence
of keratinocytes to the epidermal basement membrane. Nidogen, collagen
IV, and laminins are components of the basement membrane, integrins
are cell adhesion molecules, and tenascin-C is a matrix protein.
The expression of TGF-β receptors I and II was studied
in normal epidermis and lesional and non-lesional psoriatic epidermis
by immunohistochemistry. TGF-β1 and TGF-β2 in
suction blister fluid and serum were determined by enzyme-linked
immunoassay. Suction blister fluid and serum samples were obtained
from acne patients before and after oral isotretinoin treatment.
Suction blister fluid samples were also obtained from healthy volunteers
in two age groups from a control site and a betamethasone-pretreated
site. The expression of BP180, BP230, plectin/HD1, α6
integrin, β4 integrin, laminin 5, collagen VII, collagen
IV, nidogen, laminin α3 chain, and laminin β1g1
chains was studied in uninvolved dermatitis herpetiformis skin by
the immunofluorescence technique. The ultrastructure of the hemidesmosomal
inner plaque was studied in uninvolved dermatitis herpetiformis
skin by electron microscopy. The suction blister method was used
to study intact blisters, open wounds (=blister roofs removed
right after blister induction) and calcipotriol-pretreated open
wounds in healthy volunteers. The reepithelialization rate and the
expression of BP180, BP230, plectin/HD1, β4 integrin,
laminin 5, collagen VII, laminin α5 chain, laminin β1
chain, tenascin-C, αvβ5 integrin, β5
integrin, α5 integrin, and α9 integrin during
reepithelialization were studied by haematoxylin and eosin stainings
and the immunofluorescence technique. BP180, BP230, and plectin/HD1
expression were analyzed by body site to exclude regional variation.
In normal epidermis, TGF-β receptors I and II were
detected in the basal epidermis. Diffusion calculations suggest
that circulation is likely to be a major source of TGF-β for
TGF-β receptors in the basal epidermis. Downregulation
of TGF-β receptors I and II was seen in lesional psoriatic epidermis,
suggesting that hyperproliferating lesional epidermis may have lost
TGF-β-mediated growth inhibition. Isotretinoin did not
affect the serum TGF-β1 or TGF-β2 levels, but
caused a 19% local increase in suction blister fluid TGF-β1.
Betamethasone caused a 17% decrease in suction blister
fluid TGF-β1, presumably due to glucocorticoid-induced
vasoconstriction. Modulation of the interstitial fluid TGF-β1
concentration may be one mechanism by which isotretinoin and betamethasone
mediate their effects in skin. Immunoreactivity for BP230 and plectin/HD1
was decreased in the basement membrane zone in uninvolved dermatitis
herpetiformis skin in a significant proportion of the patients,
suggesting distinct molecular changes in BP230 and plectin/HD1.
This may be a factor contributing to blister formation. Reepithelialization
rate was considerably slower in intact blisters than in open wounds
and was not affected by calcipotriol. BP230 and plectin/HD1 appeared
earlier in intact blisters than in open wounds. Reepithelialization
took place on a continuous laminin sheath in intact blisters, but
the laminin sheath in open wounds was partially discontinuous. It
was a novel finding that integrin αvβ5 and integrin β5
antibodies showed divergent distributions in regenerating epidermis.
The present results suggest that, in some bullous diseases, removal
of the blister roof could accelerate blister healing, calcipotriol
treatment does not delay wound epithelialization, a continuous laminin
sheath may inhibit reepithelialization, and the formation of the hemidesmosomal
inner plaque at the leading edge takes place earlier in the more
slowly reepithelializing intact blisters than in open wounds.
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Pawar, Sangita. "Regulation of Integrin Alpha 6 Cleavage in Cancer." Diss., The University of Arizona, 2006. http://hdl.handle.net/10150/194296.
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Cancer metastasis is a multi-stage process initiated by the cancer cell acquiring the ability to migrate. The protein profile of such a cell undergoes dramatic changes including changes in integrin expression. Integrins play a major role in cell adhesion, motility, differentiation, blood clotting, tissue organization and cell growth as well as cancer cell migration, invasion and metastasis. Integrin a6, which can pair with integrin b4 or b1 is a laminin receptor and is detected in epithelial cells. Earlier studies have reported uPA mediated integrin a6 cleavage in prostate cancer resulting in loss of the ligand binding domain. Site-directed mutagenesis studies have identified the cleavage site to be at R594R595 located in the "stalk" region of the integrin a6. Prostate cancer cells PC3N-a6-RR cells, bearing a R594R595 to A594A595 mutation, engineered to express the uncleavable form of integrin a6 were found to migrate 6.4 folds lesser on Laminin-1 as compared to the PC3N-a6-WT cells which expressed the wild-type integrin a6. This result suggests that integrin a6 cleavage enhances migration. Prostate cancer is known to metastasize to the bone. Injection of the PC3N-a6-WT cells in mouse femurs resulted in increased bone destruction and pain behavior when compared to the femurs injected with PC3N-a6-RR cells indicating that the integrin a6 cleavage could affect and modify the bone microenvironment. An observation that complete conversion of integrin a6 to a6p was not observed in cell lines even in presence of excess uPA suggested a regulatory mechanism. Integrins are known to associate with many proteins including tetraspanins, which are transmembrane proteins, that function as protein adapters. Integrin a6 was found to be refractory to uPA mediated cleavage when complexed with tetraspanin CD151. The amount of integrin a6 available for cleavage increased when CD151 levels were decreased by CD151 siRNA treatment. These results suggest that the integrin a6 available and unavailable for cleavage can be modulated by interaction with CD151 and hence affect the migratory potential of the cell. Collectively these data suggest that integrin a6 cleavage can enhance cell migration, initiate signals to modify the tumor microenvironment and can be regulated by interaction with tetraspanin CD151.
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McMillan, James Robert. "Hemidesmosomes in human skin development and disease." Thesis, King's College London (University of London), 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.265693.
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Faure, Emilie. "Rôle de la signalisation purinergique dans la régulation de la migration des kératinocytes." Thesis, Aix-Marseille, 2012. http://www.theses.fr/2012AIXM4753/document.
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L'épiderme est un tissu stratifié, majoritairement constitué de kératinocytes qui forme la première barrière de l'organisme contre les agressions extérieures. Après blessure cutanée, la migration des kératinocytes est une phase cruciale de la cicatrisation. Le comportement des kératinocytes est placé sous le contrôle des molécules de la matrice extracellulaire ainsi que par les facteurs solubles (facteurs de croissance et cytokines..) sécrétés dans le microenvironnement. Les cellules résidentes ou recrutées sur le site de lésion libèrent également des nucléotides extracellulaires (ATP, UTP) dans l'environnement des kératinocytes. Dans ce travail de thèse, nous avons examiné l'impact des nucléotides extracellulaires et du récepteur purinergique P2Y2 sur la migration des kératinocytes et sur l'activité motogénique de deux facteurs de croissance, l'IGF-I et de l'EGF. Dans un premier temps, nous avons pu montrer que l'activation de P2Y2 et de la protéine hétérotrimérique Gαq inhibe l'activité de l'isoforme p110α de la PI3K sur des cellules stimulées par l'IGF. Cette inhibition de la voie PI3K/Akt aboutit à une perturbation de la mobilisation de la cortactine et de la formation des lamellipodes ainsi qu'une diminution de la vitesse de migration des kératinocytes. Dans un second temps, nous avons mis en évidence que l'activation de P2Y2 inhibe l'activation de la voie ERK1/2 par l'EGF en inhibant la phosphorylation des protéines MEK1/2, ERK1/2 et p90RSK. Nous avons établi que la conséquence de cette inhibition est la stabilisation des hémidesmosomes<br>The epidermis is a stratified tissue, mainly composed of keratinocytes, that forms the first barrier of the organism. When skin injury occurs, the epidermis structure is altered and many signalling pathways are activated in order to re-establish its homeostasis. Among these signalling pathways, the PI3K and MAPK ERK1/2 pathways play key roles by controlling keratinocyte migration and proliferation. The aim of this thesis was to analyse the regulation of these two signalling pathways by extracellular nucleotides, acting through purinergic receptors P2Y2 and the heterotrimeric Gαq protein and to evaluate the impact of this receptor on keratinocyte migration. Firstly, we showed that P2Y2 receptor activation inhibits PI3K p110α isoform and consequently alters keratinocyte cell shape and migration. Additionally, we showed that purinergic signalling activation inhibits EGF-induced ERK1/2 pathway activation by inhibiting the phosphorylation of MEK1/2, ERK1/2 and p90RSK proteins. As a consequence, P2Y2 stabilizes α6β4 integrin localisation into hemidesmosome-like structures and inhibits keratinocyte migration. The involvement of purinergic signalling pathway in regulation of different signalling events suggests that it may play a central role in regulation of cellular events that occurred during skin wound healing process. Moreover, our present data in association with those of the literature show that extracellular nucleotides can act as a double-edged sword in the regulation of cell migration: either activate or block cell migration in a striking cell-specific manner
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Sampaio, Rita de Cássia de Lima [UNESP]. "Laminite experimental: aspectos morfológicos, morfométricos e ultra-estruturais das lâminas dérmicas e epidérmicas do casco de eqüinos tratados com a trinitroglicerina." Universidade Estadual Paulista (UNESP), 2007. http://hdl.handle.net/11449/101144.
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sampaio_rcl_dr_jabo.pdf: 2084812 bytes, checksum: 58460a9359272871dda4cd09bd01ae62 (MD5)<br>Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)<br>Universidade Estadual Paulista (UNESP)<br>As alterações ultra-estruturais ocorridas nas lâminas epidérmicas e dérmicas de eqüinos com laminite são responsáveis pela rotação ou afundamento da falange distal dentro do casco. Com o objetivo de prevenir esta ocorrência foram estudados os efeitos da sobrecarga de carboidratos (SCHO), assim como da utilização de trinitroglicerina na fase prodrômica da laminite, nas lâminas epidérmicas do casco de quinze eqüinos. A indução da laminite por meio da sobrecarga de carboidratos alterou siginificativamente as lâminas epidérmicas primárias e secundárias dos cascos dos eqüinos dos grupos induzidos (Grupo Laminite e Grupo Laminite + Trinitroglicerina) em comparação com o Grupo Controle, causando retração das lâminas epidérmicas primárias, alongamento das lâminas epidérmicas secundárias e estreitamento das lâminas epidérmicas primárias e secundárias. A indução da laminite por meio da sobrecarga de carboidratos diminuiu significativamente a área da célula basal assim como a área do núcleo dos dois grupos induzidos (Grupo Laminite e Grupo Laminite + Trinitroglicerina) em comparação com o grupo controle. Foi observado, pela análise estatística, que o Grupo Laminite obteve maior redução das áreas, tanto da célula como do núcleo, porém a porcentagem de ocupação do núcleo na célula não foi diferente nos dois grupos induzidos. Na avaliação histopatológica, foram observadas lesões lamelares nos grupos Laminite e Laminite + Trinitroglicerina, características de processo degenerativo das lâminas epidérmicas. Ocorreram diminuições nos números de hemidesmossomos dos grupos induzidos quando comparados com o Grupo Controle. A administração de trinitroglicerina não foi capaz de impedir o desenvolvimento de lesões nas lâminas epidérmicas e dérmicas, assim como, nas células basais e membrana basal em cavalos com laminite induzida por sobrecarga de carboidratos.<br>Disruption of the lamellar ultrastructural is responsible for a cellular failure, that culminates in distal rotation of the distal phalanx within the hoof. Aiming to prevent such debilitating condition, effects of carbohydrate overload and glyceryl trinitrate (TNG) use during the prodromal stages of experimentally induced laminitis in fifteen horses hoof were studied. Laminitis induced by grain overload affected significantly primary and secondary lamellar structure from horse´s hoof (Group II and III), which in turn led to primary epidermal retraction, basal cells became elongated and both primary and secondary epidermal lamellae clump together when compared to control group (GI). Equine that developed laminitis induced by carbohydrate overload had a significant reduction in basal cell nucleus in both GII and GIII groups, when compared to horses from GI. Horses from GII group had higher reduction in areas relative to both cell and nucleus, however, the percentage of nucleus position within cell was not different in both horses groups (GII and GIII). Histophatology of hooves revealed lamellae lesions in both horses groups (GII and GIII), characterized by a degenerative process present on epidermal lamellae. Lower number of hemidesmosome in both GII and GIII groups were observed. The administration of TNG was unable to prevent the development of lesions lamellae epidermal and dermal, as in the epidermal basal cells and the basement membrane in horses with laminitis induced by carbohydrate overload.
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Sampaio, Rita de Cássia de Lima. "Laminite experimental: aspectos morfológicos, morfométricos e ultra-estruturais das lâminas dérmicas e epidérmicas do casco de eqüinos tratados com a trinitroglicerina /." Jaboticabal : [s.n.], 2007. http://hdl.handle.net/11449/101144.
Full textAbstract:
Resumo: As alterações ultra-estruturais ocorridas nas lâminas epidérmicas e dérmicas de eqüinos com laminite são responsáveis pela rotação ou afundamento da falange distal dentro do casco. Com o objetivo de prevenir esta ocorrência foram estudados os efeitos da sobrecarga de carboidratos (SCHO), assim como da utilização de trinitroglicerina na fase prodrômica da laminite, nas lâminas epidérmicas do casco de quinze eqüinos. A indução da laminite por meio da sobrecarga de carboidratos alterou siginificativamente as lâminas epidérmicas primárias e secundárias dos cascos dos eqüinos dos grupos induzidos (Grupo Laminite e Grupo Laminite + Trinitroglicerina) em comparação com o Grupo Controle, causando retração das lâminas epidérmicas primárias, alongamento das lâminas epidérmicas secundárias e estreitamento das lâminas epidérmicas primárias e secundárias. A indução da laminite por meio da sobrecarga de carboidratos diminuiu significativamente a área da célula basal assim como a área do núcleo dos dois grupos induzidos (Grupo Laminite e Grupo Laminite + Trinitroglicerina) em comparação com o grupo controle. Foi observado, pela análise estatística, que o Grupo Laminite obteve maior redução das áreas, tanto da célula como do núcleo, porém a porcentagem de ocupação do núcleo na célula não foi diferente nos dois grupos induzidos. Na avaliação histopatológica, foram observadas lesões lamelares nos grupos Laminite e Laminite + Trinitroglicerina, características de processo degenerativo das lâminas epidérmicas. Ocorreram diminuições nos números de hemidesmossomos dos grupos induzidos quando comparados com o Grupo Controle. A administração de trinitroglicerina não foi capaz de impedir o desenvolvimento de lesões nas lâminas epidérmicas e dérmicas, assim como, nas células basais e membrana basal em cavalos com laminite induzida por sobrecarga de carboidratos.<br>Abstract: Disruption of the lamellar ultrastructural is responsible for a cellular failure, that culminates in distal rotation of the distal phalanx within the hoof. Aiming to prevent such debilitating condition, effects of carbohydrate overload and glyceryl trinitrate (TNG) use during the prodromal stages of experimentally induced laminitis in fifteen horses hoof were studied. Laminitis induced by grain overload affected significantly primary and secondary lamellar structure from horse's hoof (Group II and III), which in turn led to primary epidermal retraction, basal cells became elongated and both primary and secondary epidermal lamellae clump together when compared to control group (GI). Equine that developed laminitis induced by carbohydrate overload had a significant reduction in basal cell nucleus in both GII and GIII groups, when compared to horses from GI. Horses from GII group had higher reduction in areas relative to both cell and nucleus, however, the percentage of nucleus position within cell was not different in both horses groups (GII and GIII). Histophatology of hooves revealed lamellae lesions in both horses groups (GII and GIII), characterized by a degenerative process present on epidermal lamellae. Lower number of hemidesmosome in both GII and GIII groups were observed. The administration of TNG was unable to prevent the development of lesions lamellae epidermal and dermal, as in the epidermal basal cells and the basement membrane in horses with laminitis induced by carbohydrate overload.<br>Orientador: José Correa de Lacerda Neto<br>Coorientadora: Silvana Martinez Baraldi Artoni<br>Banca: Antonio Cezar de Oliveira Dearo<br>Banca: Raquel Yvonne Arantes Baccarin<br>Banca: José Wanderley Cattelan<br>Banca: Marcos Lania de Araujo<br>Doutor
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Draheim, Kyle M. "An Integral Role of ARRDC3 in Stem Cell Migration and Breast Cancer Progression: A Dissertation." eScholarship@UMMS, 2010. https://escholarship.umassmed.edu/gsbs_diss/468.
Full textAbstract:
Despite the importance of integrins in epithelial cell biology surprisingly little is known about their regulation. It is known that they form hemidesmosomes (HDs), are actively involved in cell contacts during cell migration/invasion, and are key signaling molecules for survival and growth. However, there has been a distinct lack of understanding about what controls the dynamic integrin localization during cell activation and movement. Growth factors, such as EGF, are elevated during wound healing and carcinoma invasion leading to phosphorylation of ITGβ4 and the disassembly of the HD and mobilization of ITGβ4 to actin-rich protrusions. More recently the phosphorylation of a novel site on ITGβ4 (S1424) was found to be distinctly enriched on the trailing edge of migrating cells, suggesting a possible mechanism for the dissociation of ITGβ4 from HDs.
Arrestin family member proteins are involved in the regulation of cell surface proteins and vesicular trafficking. In this study, we find that over-expression of arrestin family member ARRDC3 causes internalization and proteosome-dependent degradation of ITGβ4, while decreased levels of ARRDC3 stabilizes ITGβ4 levels. These results lead us to a new mechanism of ITGβ4 internalization, trafficking and degradation. During migration, ARRDC3 co-localizes with ITGβ4 on the lagging edge of cells but has a distinct distribution on the leading edge of cells. Additional immuno co-precipitation experiments demonstrate that ARRDC3 preferentially binds to ITGβ4 when phosphorylated on S1424. Using confocal microscopy, we show that the expression pattern of ARRDC3 on the lagging edge of a migrating cell is identical to the expression pattern of ITGβ4-pS1424. We demonstrate that ARRDC3 expression represses cell proliferation, migration, invasion, growth in soft agar and tumorigenicity.
Collectively, our data reveals that ARRDC3 is a negative regulator of β4 integrin and demonstrates how this new pathway impacts biologic processes in stem cell and cancer biology. Additionally, as ARRDC3 is highly expressed in several tissues and conserved across species, our results are likely to be translated to other models.
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"Biochemical and ultrastructural analyses of BP180(Type XVII collagen),a transmembrane collagenous protein of the hemidesmosome." Thesis, 1998. http://hdl.handle.net/2237/6461.
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Hirako, Yoshiaki, and 善章 平子. "Biochemical and ultrastructural analyses of BP180(Type XVII collagen),a transmembrane collagenous protein of the hemidesmosome." Thesis, 1998. http://hdl.handle.net/2237/6461.
Full textBooks on the topic "Hemidesmosome"
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E, Collins Jane, and Garrod D. R, eds. Molecular biology of desmosomes and hemidesmosomes. R.G. Landes Co., 1994.
Find full textBook chapters on the topic "Hemidesmosome"
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Klingeborn, Mikael, and Emily D. Reese. "Desmosome and Hemidesmosome Disassembly in Retinal Pigmented Epithelium: Intersection with the Exosome Pathway." In Advances in Experimental Medicine and Biology. Springer Nature Switzerland, 2025. https://doi.org/10.1007/978-3-031-76550-6_56.
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Turcan, Iana, Maria C. Bolling, and Marcel F. Jonkman. "Structure of Hemidesmosomes and the Epidermal Basement Membrane Zone." In Autoimmune Bullous Diseases. Springer International Publishing, 2022. http://dx.doi.org/10.1007/978-3-030-91557-5_13.
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Turcan, Iana, and Marcel F. Jonkman. "Structure of Hemidesmosomes and the Epidermal Basement Membrane Zone." In Autoimmune Bullous Diseases. Springer International Publishing, 2015. http://dx.doi.org/10.1007/978-3-319-23754-1_13.
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Koster, J., L. Borradori, and A. Sonnenberg. "Hemidesmosomes: Molecular Organization and Their Importance for Cell Adhesion and Disease." In Handbook of Experimental Pharmacology. Springer Berlin Heidelberg, 2004. http://dx.doi.org/10.1007/978-3-540-68170-0_9.
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Pavelka, Margit, and Jürgen Roth. "Skin Basement Membrane and Keratinocyte Hemidesmosomes: An Epithel-Connective Tissue Junctional Complex." In Functional Ultrastructure. Springer Vienna, 2010. http://dx.doi.org/10.1007/978-3-211-99390-3_98.
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Selby, John C. "Mechanobiology of Epidermal Keratinocytes: Desmosomes, Hemidesmosomes, Keratin Intermediate Filaments, and Blistering Skin Diseases." In Mechanobiology of Cell-Cell and Cell-Matrix Interactions. Springer US, 2011. http://dx.doi.org/10.1007/978-1-4419-8083-0_9.
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"Hemidesmosome." In Encyclopedia of Parasitology. Springer Berlin Heidelberg, 2016. http://dx.doi.org/10.1007/978-3-662-43978-4_1432.
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Dowling, James, and Elaine Fuchs. "BPAG1." In Guidebook to the Cytoskeletal and Motor Proteins. Oxford University PressOxford, 1999. http://dx.doi.org/10.1093/oso/9780198599579.003.00106.
Full textAbstract:
Abstract The BPAG1 gene locus encodes two major isoforms which share a common C terminal intermediate filament binding domain. The 230 kDa epidermal splice variant, BPAG1e, is a major component of the inner plaque portion of the hemidesmosome and is required for stable interaction of this junction with keratin filaments. The 280 kDa neuronal isoform, BPAG1 n, contains a bona fide actin-binding domain in addition to the intermediate filament binding domain and is essential for primary sensory neurone function. Both BPAG1e and BPAG1n are members of a growing family of intermediate filament linker proteins that also includes desmoplakin, envoplakin, and plectin.
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"HEMIDESMOSOMES." In Epithelial Morphogenesis in Development and Disease. CRC Press, 2003. http://dx.doi.org/10.1201/b20586-10.
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Todorović, V., K. R. Kligys, R. L. Dusek, J. C. R. Jones, and K. J. Green. "Desmosomes and Hemidesmosomes." In Encyclopedia of Biological Chemistry. Elsevier, 2013. http://dx.doi.org/10.1016/b978-0-12-378630-2.00472-2.
Full textConference papers on the topic "Hemidesmosome"
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Laval, Séverine, Hanane Laklai, Marjorie FanJul, et al. "Abstract 5181: Forced hemidesmosome assembly blocks pancreatic cancer cell invasiveness." In Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC. American Association for Cancer Research, 2010. http://dx.doi.org/10.1158/1538-7445.am10-5181.
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Laval, Séverine, Mounira Chalabi, Hanane Laklai, et al. "Abstract B60: Critical role of hemidesmosome breakdown for human pancreatic cancer cell migration and invasion." In Abstracts: AACR Special Conference on Pancreatic Cancer: Progress and Challenges; June 18-21, 2012; Lake Tahoe, NV. American Association for Cancer Research, 2012. http://dx.doi.org/10.1158/1538-7445.panca2012-b60.
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Greenwood, E., P. Cane Gasull, B. Moore, and K. Cheung. "Abstract P1-01-14: The hemidesmosome protein collagen 17A1 is required for collective invasion and growth of mammary tumor organoids." In Abstracts: 2017 San Antonio Breast Cancer Symposium; December 5-9, 2017; San Antonio, Texas. American Association for Cancer Research, 2018. http://dx.doi.org/10.1158/1538-7445.sabcs17-p1-01-14.
Full textReports on the topic "Hemidesmosome"
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dePereda, José María. Hemidesmosomas: tornillos moleculares que sujetan nuestra piel. Sociedad Española de Bioquímica y Biología Molecular, 2018. http://dx.doi.org/10.18567/sebbmdiv_rpc.2018.05.1.
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Christiano, Angela M. Development of Genetic Therapies for the Hemidesmosomal Subtypes of Junctional Epidermolysis Bullosa. Defense Technical Information Center, 2001. http://dx.doi.org/10.21236/ada410899.
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Christiano, Angela M. Development of Genetic Therapies for the Hemidesmosomal Subtypes of Junctional Epidermolysis Bullosa. Defense Technical Information Center, 2002. http://dx.doi.org/10.21236/ada411310.
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