Skip to main content

ORIGINAL RESEARCH article

Front. Mol. Biosci.
Sec. Cellular Biochemistry
Volume 11 - 2024 | doi: 10.3389/fmolb.2024.1442611

The downregulation of tight junction proteins and pIgR in the colonic epithelium causes the susceptibility of EpCAM +/-mice to colitis and gut microbiota dysbiosis

Provisionally accepted
Ya Nie Ya Nie Ting Lin Ting Lin Yanhong Yang Yanhong Yang Wanwan Liu Wanwan Liu Qing Hu Qing Hu Chen Guibin Chen Guibin Li Huang Li Huang Huijuan Wu Huijuan Wu Cunjie Kong Cunjie Kong Zili Lei Zili Lei *Jiao Guo Jiao Guo
  • Guangdong Pharmaceutical University, Guangzhou, China

The final, formatted version of the article will be published soon.

    The genetic factors play important roles on the pathogenesis of inflammatory bowel disease (IBD). EpCAM is highly expressed in the intestinal epithelium. It is still unclear if the decrease or somatic mutation of EpCAM could cause IBD. The WT and EpCAM +/-mice were administrated with DSS intermittently for nearly 8 weeks. The colon, liver and feces were harvested to check the morphological and histological changes, the expression of inflammatory genes and the gut microbiota via H&E staining, immunofluorescence, qPCR, western blot and 16S rDNA sequence assays. The DSS administration induced more serious inflammation in the colon of EpCAM +/-mice than WT mice. Compared to DSS-induced WT mice, the transcriptional levels of IL-6, F4/80, Ly6g, Ly6d and Igha were significantly higher in the colon of DSS-induced EpCAM +/-mice. The protein levels of MMP7 and MMP8 and the activation of JNK, ERK1/2 and p38 were significantly increased in the colon of DSS-induced EpCAM +/-mice. The protein levels of CLDN1, CLDN2, CLDN3, CLDN7, OCLD, ZO-1 and pIgR were significantly decreased in the colon of DSS-induced EpCAM +/-mice. The serum concentration of LPS was significantly higher in the DSS-induced EpCAM +/-mice which caused the acute inflammation in the liver of them. The expression of Pigr was significantly reduced in the liver of DSS-induced EpCAM +/-mice. The ratio of Firmicutes/Bacteroidetes at the phylum level was higher in the gut microbiota of EpCAM +/-mice than WT mice. In conclusion, the heterozygous mutation of EpCAM increased the susceptibility to colitis, gut microbiota dysbiosis and liver injury.

    Keywords: EpCAM 1, inflammatory bowel disease 2, Tight junction 3, pIgR 4, gut microbiota 5

    Received: 02 Jun 2024; Accepted: 29 Jul 2024.

    Copyright: © 2024 Nie, Lin, Yang, Liu, Hu, Guibin, Huang, Wu, Kong, Lei and Guo. 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) or licensor 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.

    * Correspondence: Zili Lei, Guangdong Pharmaceutical University, Guangzhou, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.