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Adrenomedullin alleviates mucosal injury in experimental colitis and increases claudin‐4 expression in the colonic epithelium

Adrenomedullin (AM) is a peptide with pleiotropic physiological functions that attenuates intestinal mucosal inflammation. However, the mechanism underpinning mucosal protection by AM is not fully understood, and its effect on intestinal epithelial cells remains unclear. Here, we investigated the ef...

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Autores principales: Kawaguchi, Makiko, Kataoka, Hiroaki, Kiwaki, Takumi, Weiting, Liang, Nagata, Sayaka, Kitamura, Kazuo, Fukushima, Tsuyoshi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10068314/
https://www.ncbi.nlm.nih.gov/pubmed/36799102
http://dx.doi.org/10.1002/2211-5463.13577
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author Kawaguchi, Makiko
Kataoka, Hiroaki
Kiwaki, Takumi
Weiting, Liang
Nagata, Sayaka
Kitamura, Kazuo
Fukushima, Tsuyoshi
author_facet Kawaguchi, Makiko
Kataoka, Hiroaki
Kiwaki, Takumi
Weiting, Liang
Nagata, Sayaka
Kitamura, Kazuo
Fukushima, Tsuyoshi
author_sort Kawaguchi, Makiko
collection PubMed
description Adrenomedullin (AM) is a peptide with pleiotropic physiological functions that attenuates intestinal mucosal inflammation. However, the mechanism underpinning mucosal protection by AM is not fully understood, and its effect on intestinal epithelial cells remains unclear. Here, we investigated the effects of AM on junctional molecules in primary‐cultured murine intestinal epithelial cells and discovered that AM upregulates claudin‐4 expression. In a mouse model of dextran sulfate sodium‐induced colitis, AM administration also enhanced claudin‐4 expression and accelerated mucosal regeneration. Furthermore, AM reversed TNFα‐mediated downregulation of claudin‐4 and loss of cell–cell adhesion of the HCT116 human intestinal epithelial cell line in vitro. These results indicate that AM may enhance intestinal epithelial integrity by upregulating claudin‐4 expression.
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spelling pubmed-100683142023-04-04 Adrenomedullin alleviates mucosal injury in experimental colitis and increases claudin‐4 expression in the colonic epithelium Kawaguchi, Makiko Kataoka, Hiroaki Kiwaki, Takumi Weiting, Liang Nagata, Sayaka Kitamura, Kazuo Fukushima, Tsuyoshi FEBS Open Bio Research Articles Adrenomedullin (AM) is a peptide with pleiotropic physiological functions that attenuates intestinal mucosal inflammation. However, the mechanism underpinning mucosal protection by AM is not fully understood, and its effect on intestinal epithelial cells remains unclear. Here, we investigated the effects of AM on junctional molecules in primary‐cultured murine intestinal epithelial cells and discovered that AM upregulates claudin‐4 expression. In a mouse model of dextran sulfate sodium‐induced colitis, AM administration also enhanced claudin‐4 expression and accelerated mucosal regeneration. Furthermore, AM reversed TNFα‐mediated downregulation of claudin‐4 and loss of cell–cell adhesion of the HCT116 human intestinal epithelial cell line in vitro. These results indicate that AM may enhance intestinal epithelial integrity by upregulating claudin‐4 expression. John Wiley and Sons Inc. 2023-02-27 /pmc/articles/PMC10068314/ /pubmed/36799102 http://dx.doi.org/10.1002/2211-5463.13577 Text en © 2023 The Authors. FEBS Open Bio published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Kawaguchi, Makiko
Kataoka, Hiroaki
Kiwaki, Takumi
Weiting, Liang
Nagata, Sayaka
Kitamura, Kazuo
Fukushima, Tsuyoshi
Adrenomedullin alleviates mucosal injury in experimental colitis and increases claudin‐4 expression in the colonic epithelium
title Adrenomedullin alleviates mucosal injury in experimental colitis and increases claudin‐4 expression in the colonic epithelium
title_full Adrenomedullin alleviates mucosal injury in experimental colitis and increases claudin‐4 expression in the colonic epithelium
title_fullStr Adrenomedullin alleviates mucosal injury in experimental colitis and increases claudin‐4 expression in the colonic epithelium
title_full_unstemmed Adrenomedullin alleviates mucosal injury in experimental colitis and increases claudin‐4 expression in the colonic epithelium
title_short Adrenomedullin alleviates mucosal injury in experimental colitis and increases claudin‐4 expression in the colonic epithelium
title_sort adrenomedullin alleviates mucosal injury in experimental colitis and increases claudin‐4 expression in the colonic epithelium
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10068314/
https://www.ncbi.nlm.nih.gov/pubmed/36799102
http://dx.doi.org/10.1002/2211-5463.13577
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