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Chitinase 3-like 1 induces survival and proliferation of intestinal epithelial cells during chronic inflammation and colitis-associated cancer by regulating S100A9

Many host-factors are inducibly expressed during the development of inflammatory bowel disease (IBD), each having their unique properties, such as immune activation, bacterial clearance, and tissue repair/remodeling. Dysregulation/imbalance of these factors may have pathogenic effects that can contr...

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Autores principales: Low, Daren, Subramaniam, Renuka, Lin, Li, Aomatsu, Tomoki, Mizoguchi, Atsushi, Ng, Aylwin, DeGruttola, Arianna K., Lee, Chun Geun, Elias, Jack A., Andoh, Akira, Mino-Kenudson, Mari, Mizoguchi, Emiko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4742194/
https://www.ncbi.nlm.nih.gov/pubmed/26431492
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author Low, Daren
Subramaniam, Renuka
Lin, Li
Aomatsu, Tomoki
Mizoguchi, Atsushi
Ng, Aylwin
DeGruttola, Arianna K.
Lee, Chun Geun
Elias, Jack A.
Andoh, Akira
Mino-Kenudson, Mari
Mizoguchi, Emiko
author_facet Low, Daren
Subramaniam, Renuka
Lin, Li
Aomatsu, Tomoki
Mizoguchi, Atsushi
Ng, Aylwin
DeGruttola, Arianna K.
Lee, Chun Geun
Elias, Jack A.
Andoh, Akira
Mino-Kenudson, Mari
Mizoguchi, Emiko
author_sort Low, Daren
collection PubMed
description Many host-factors are inducibly expressed during the development of inflammatory bowel disease (IBD), each having their unique properties, such as immune activation, bacterial clearance, and tissue repair/remodeling. Dysregulation/imbalance of these factors may have pathogenic effects that can contribute to colitis-associated cancer (CAC). Previous reports showed that IBD patients inducibly express colonic chitinase 3-like 1 (CHI3L1) that is further upregulated during CAC development. However, little is known about the direct pathogenic involvement of CHI3L1 in vivo. Here we demonstrate that CHI3L1 (aka Brp39) knockout (KO) mice treated with azoxymethane (AOM)/dextran sulphate sodium (DSS) developed severe colitis but lesser incidence of CAC as compared to that in wild-type (WT) mice. Highest CHI3L1 expression was found during the chronic phase of colitis, rather than the acute phase, and is essential to promote intestinal epithelial cell (IEC) proliferation in vivo. This CHI3L1-mediated cell proliferation/survival involves partial downregulation of the pro-apoptotic S100A9 protein that is highly expressed during the acute phase of colitis, by binding to the S100A9 receptor, RAGE (Receptor for Advanced Glycation End products). This interaction disrupts the S100A9-associated expression positive feedback loop during early immune activation, creating a CHI3L1(hi) S100A9(low) colonic environment, especially in the later phase of colitis, which promotes cell proliferation/survival of both normal IECs and tumor cells.
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spelling pubmed-47421942016-04-04 Chitinase 3-like 1 induces survival and proliferation of intestinal epithelial cells during chronic inflammation and colitis-associated cancer by regulating S100A9 Low, Daren Subramaniam, Renuka Lin, Li Aomatsu, Tomoki Mizoguchi, Atsushi Ng, Aylwin DeGruttola, Arianna K. Lee, Chun Geun Elias, Jack A. Andoh, Akira Mino-Kenudson, Mari Mizoguchi, Emiko Oncotarget Research Paper Many host-factors are inducibly expressed during the development of inflammatory bowel disease (IBD), each having their unique properties, such as immune activation, bacterial clearance, and tissue repair/remodeling. Dysregulation/imbalance of these factors may have pathogenic effects that can contribute to colitis-associated cancer (CAC). Previous reports showed that IBD patients inducibly express colonic chitinase 3-like 1 (CHI3L1) that is further upregulated during CAC development. However, little is known about the direct pathogenic involvement of CHI3L1 in vivo. Here we demonstrate that CHI3L1 (aka Brp39) knockout (KO) mice treated with azoxymethane (AOM)/dextran sulphate sodium (DSS) developed severe colitis but lesser incidence of CAC as compared to that in wild-type (WT) mice. Highest CHI3L1 expression was found during the chronic phase of colitis, rather than the acute phase, and is essential to promote intestinal epithelial cell (IEC) proliferation in vivo. This CHI3L1-mediated cell proliferation/survival involves partial downregulation of the pro-apoptotic S100A9 protein that is highly expressed during the acute phase of colitis, by binding to the S100A9 receptor, RAGE (Receptor for Advanced Glycation End products). This interaction disrupts the S100A9-associated expression positive feedback loop during early immune activation, creating a CHI3L1(hi) S100A9(low) colonic environment, especially in the later phase of colitis, which promotes cell proliferation/survival of both normal IECs and tumor cells. Impact Journals LLC 2015-09-28 /pmc/articles/PMC4742194/ /pubmed/26431492 Text en Copyright: © 2015 Low et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Low, Daren
Subramaniam, Renuka
Lin, Li
Aomatsu, Tomoki
Mizoguchi, Atsushi
Ng, Aylwin
DeGruttola, Arianna K.
Lee, Chun Geun
Elias, Jack A.
Andoh, Akira
Mino-Kenudson, Mari
Mizoguchi, Emiko
Chitinase 3-like 1 induces survival and proliferation of intestinal epithelial cells during chronic inflammation and colitis-associated cancer by regulating S100A9
title Chitinase 3-like 1 induces survival and proliferation of intestinal epithelial cells during chronic inflammation and colitis-associated cancer by regulating S100A9
title_full Chitinase 3-like 1 induces survival and proliferation of intestinal epithelial cells during chronic inflammation and colitis-associated cancer by regulating S100A9
title_fullStr Chitinase 3-like 1 induces survival and proliferation of intestinal epithelial cells during chronic inflammation and colitis-associated cancer by regulating S100A9
title_full_unstemmed Chitinase 3-like 1 induces survival and proliferation of intestinal epithelial cells during chronic inflammation and colitis-associated cancer by regulating S100A9
title_short Chitinase 3-like 1 induces survival and proliferation of intestinal epithelial cells during chronic inflammation and colitis-associated cancer by regulating S100A9
title_sort chitinase 3-like 1 induces survival and proliferation of intestinal epithelial cells during chronic inflammation and colitis-associated cancer by regulating s100a9
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4742194/
https://www.ncbi.nlm.nih.gov/pubmed/26431492
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