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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...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2015
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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. |
format | Online Article Text |
id | pubmed-4569309 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
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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