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Inflammation-induced desmoglein-2 ectodomain shedding compromises the mucosal barrier

Desmosomal cadherins mediate intercellular adhesion and control epithelial homeostasis. Recent studies show that proteinases play an important role in the pathobiology of cancer by targeting epithelial intercellular junction proteins such as cadherins. Here we describe the proinflammatory cytokine-i...

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Autores principales: Kamekura, Ryuta, Nava, Porfirio, Feng, Mingli, Quiros, Miguel, Nishio, Hikaru, Weber, Dominique A., Parkos, Charles A., Nusrat, Asma
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4569309/
https://www.ncbi.nlm.nih.gov/pubmed/26224314
http://dx.doi.org/10.1091/mbc.E15-03-0147
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author Kamekura, Ryuta
Nava, Porfirio
Feng, Mingli
Quiros, Miguel
Nishio, Hikaru
Weber, Dominique A.
Parkos, Charles A.
Nusrat, Asma
author_facet Kamekura, Ryuta
Nava, Porfirio
Feng, Mingli
Quiros, Miguel
Nishio, Hikaru
Weber, Dominique A.
Parkos, Charles A.
Nusrat, Asma
author_sort Kamekura, Ryuta
collection PubMed
description Desmosomal cadherins mediate intercellular adhesion and control epithelial homeostasis. Recent studies show that proteinases play an important role in the pathobiology of cancer by targeting epithelial intercellular junction proteins such as cadherins. Here we describe the proinflammatory cytokine-induced activation of matrix metalloproteinase 9 and a disintegrin and metalloproteinase domain–containing protein 10, which promote the shedding of desmosomal cadherin desmoglein-2 (Dsg2) ectodomains in intestinal epithelial cells. Epithelial exposure to Dsg2 ectodomains compromises intercellular adhesion by promoting the relocalization of endogenous Dsg2 and E-cadherin from the plasma membrane while also promoting proliferation by activation of human epidermal growth factor receptor 2/3 signaling. Cadherin ectodomains were detected in the inflamed intestinal mucosa of mice with colitis and patients with ulcerative colitis. Taken together, our findings reveal a novel response pathway in which inflammation-induced modification of columnar epithelial cell cadherins decreases intercellular adhesion while enhancing cellular proliferation, which may serve as a compensatory mechanism to promote repair.
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spelling pubmed-45693092015-11-30 Inflammation-induced desmoglein-2 ectodomain shedding compromises the mucosal barrier Kamekura, Ryuta Nava, Porfirio Feng, Mingli Quiros, Miguel Nishio, Hikaru Weber, Dominique A. Parkos, Charles A. Nusrat, Asma Mol Biol Cell Articles Desmosomal cadherins mediate intercellular adhesion and control epithelial homeostasis. Recent studies show that proteinases play an important role in the pathobiology of cancer by targeting epithelial intercellular junction proteins such as cadherins. Here we describe the proinflammatory cytokine-induced activation of matrix metalloproteinase 9 and a disintegrin and metalloproteinase domain–containing protein 10, which promote the shedding of desmosomal cadherin desmoglein-2 (Dsg2) ectodomains in intestinal epithelial cells. Epithelial exposure to Dsg2 ectodomains compromises intercellular adhesion by promoting the relocalization of endogenous Dsg2 and E-cadherin from the plasma membrane while also promoting proliferation by activation of human epidermal growth factor receptor 2/3 signaling. Cadherin ectodomains were detected in the inflamed intestinal mucosa of mice with colitis and patients with ulcerative colitis. Taken together, our findings reveal a novel response pathway in which inflammation-induced modification of columnar epithelial cell cadherins decreases intercellular adhesion while enhancing cellular proliferation, which may serve as a compensatory mechanism to promote repair. The American Society for Cell Biology 2015-09-15 /pmc/articles/PMC4569309/ /pubmed/26224314 http://dx.doi.org/10.1091/mbc.E15-03-0147 Text en © 2015 Kamekura et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology.
spellingShingle Articles
Kamekura, Ryuta
Nava, Porfirio
Feng, Mingli
Quiros, Miguel
Nishio, Hikaru
Weber, Dominique A.
Parkos, Charles A.
Nusrat, Asma
Inflammation-induced desmoglein-2 ectodomain shedding compromises the mucosal barrier
title Inflammation-induced desmoglein-2 ectodomain shedding compromises the mucosal barrier
title_full Inflammation-induced desmoglein-2 ectodomain shedding compromises the mucosal barrier
title_fullStr Inflammation-induced desmoglein-2 ectodomain shedding compromises the mucosal barrier
title_full_unstemmed Inflammation-induced desmoglein-2 ectodomain shedding compromises the mucosal barrier
title_short Inflammation-induced desmoglein-2 ectodomain shedding compromises the mucosal barrier
title_sort inflammation-induced desmoglein-2 ectodomain shedding compromises the mucosal barrier
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4569309/
https://www.ncbi.nlm.nih.gov/pubmed/26224314
http://dx.doi.org/10.1091/mbc.E15-03-0147
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