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The mechanism of colon tissue damage mediated by HIF-1α/NF-κB/STAT1 in high-altitude environment

The high-altitude environment damages the intestinal mucosal barrier, leading to a high incidence of intestinal diseases and seriously affects the working ability of people at high altitude. However, how high altitude induces intestinal mucosal barrier injury has not been well defined. The purpose o...

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Autores principales: Cheng, Junfei, Sun, Yuemei, He, Jiaxin, Wang, Zihan, Li, Wenbin, Wang, Rong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9508275/
https://www.ncbi.nlm.nih.gov/pubmed/36164339
http://dx.doi.org/10.3389/fphys.2022.933659
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author Cheng, Junfei
Sun, Yuemei
He, Jiaxin
Wang, Zihan
Li, Wenbin
Wang, Rong
author_facet Cheng, Junfei
Sun, Yuemei
He, Jiaxin
Wang, Zihan
Li, Wenbin
Wang, Rong
author_sort Cheng, Junfei
collection PubMed
description The high-altitude environment damages the intestinal mucosal barrier, leading to a high incidence of intestinal diseases and seriously affects the working ability of people at high altitude. However, how high altitude induces intestinal mucosal barrier injury has not been well defined. The purpose of this study was to investigate the mechanism of colonic tissue injury induced by the influence of the high-altitude environment on the colonic microenvironment. Forty-eight SPF C57BL/6J mice were randomly divided into four groups: the control group and three other that were high-altitude exposure groups (Yushu, Qinghai; elevation: 4,010 m; 12 h, 24 h, 48 h). First, HE staining was used to observe the effect of the high-altitude environment on colon histomorphology of mice. The protein expression levels of claudin-1, occludin, and ZO-1 were analyzed by molecular biological methods. We found that altitude caused inflammatory damage to colon tissue. Intestinal hypoxia was measured with the hypoxic probe pimonidazole (PMDZ). Interestingly, we observed a decrease in the concentration of oxygen in the microenvironment in the colonic lumen. We sought to explore the mechanism of colonic mucosal barrier damage at different times when entering high altitude. The expression levels of hypoxia-inducible factors: HIF-1α, STAT1, and NF-κB and of inflammatory factors: IFN-γ, TNF-α, and IL-6 were significantly increased. This work highlights that the high-altitude environment leads to a reduction in the concentration of oxygen in the microenvironment of the colonic lumen, which disrupts the colonic mucosal barrier and ultimately induces and exacerbates intestinal injury.
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spelling pubmed-95082752022-09-25 The mechanism of colon tissue damage mediated by HIF-1α/NF-κB/STAT1 in high-altitude environment Cheng, Junfei Sun, Yuemei He, Jiaxin Wang, Zihan Li, Wenbin Wang, Rong Front Physiol Physiology The high-altitude environment damages the intestinal mucosal barrier, leading to a high incidence of intestinal diseases and seriously affects the working ability of people at high altitude. However, how high altitude induces intestinal mucosal barrier injury has not been well defined. The purpose of this study was to investigate the mechanism of colonic tissue injury induced by the influence of the high-altitude environment on the colonic microenvironment. Forty-eight SPF C57BL/6J mice were randomly divided into four groups: the control group and three other that were high-altitude exposure groups (Yushu, Qinghai; elevation: 4,010 m; 12 h, 24 h, 48 h). First, HE staining was used to observe the effect of the high-altitude environment on colon histomorphology of mice. The protein expression levels of claudin-1, occludin, and ZO-1 were analyzed by molecular biological methods. We found that altitude caused inflammatory damage to colon tissue. Intestinal hypoxia was measured with the hypoxic probe pimonidazole (PMDZ). Interestingly, we observed a decrease in the concentration of oxygen in the microenvironment in the colonic lumen. We sought to explore the mechanism of colonic mucosal barrier damage at different times when entering high altitude. The expression levels of hypoxia-inducible factors: HIF-1α, STAT1, and NF-κB and of inflammatory factors: IFN-γ, TNF-α, and IL-6 were significantly increased. This work highlights that the high-altitude environment leads to a reduction in the concentration of oxygen in the microenvironment of the colonic lumen, which disrupts the colonic mucosal barrier and ultimately induces and exacerbates intestinal injury. Frontiers Media S.A. 2022-09-09 /pmc/articles/PMC9508275/ /pubmed/36164339 http://dx.doi.org/10.3389/fphys.2022.933659 Text en Copyright © 2022 Cheng, Sun, He, Wang, Li and Wang. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Physiology
Cheng, Junfei
Sun, Yuemei
He, Jiaxin
Wang, Zihan
Li, Wenbin
Wang, Rong
The mechanism of colon tissue damage mediated by HIF-1α/NF-κB/STAT1 in high-altitude environment
title The mechanism of colon tissue damage mediated by HIF-1α/NF-κB/STAT1 in high-altitude environment
title_full The mechanism of colon tissue damage mediated by HIF-1α/NF-κB/STAT1 in high-altitude environment
title_fullStr The mechanism of colon tissue damage mediated by HIF-1α/NF-κB/STAT1 in high-altitude environment
title_full_unstemmed The mechanism of colon tissue damage mediated by HIF-1α/NF-κB/STAT1 in high-altitude environment
title_short The mechanism of colon tissue damage mediated by HIF-1α/NF-κB/STAT1 in high-altitude environment
title_sort mechanism of colon tissue damage mediated by hif-1α/nf-κb/stat1 in high-altitude environment
topic Physiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9508275/
https://www.ncbi.nlm.nih.gov/pubmed/36164339
http://dx.doi.org/10.3389/fphys.2022.933659
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