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Research Paper|Volume 12, Issue 14|pp 14966—14977

MiR-155 contributes to intestinal barrier dysfunction in DSS-induced mice colitis via targeting HIF-1α/TFF-3 axis

Yujin Liu1, Feng Zhu1, Huarong Li1, Heng Fan1, Hui Wu1, Yalan Dong1, Si Chu1, Chen Tan1, Quansheng Wang1, Hongxia He1, Fei Gao1, Xueyuan Leng1, Qiaoli Zhou1, Xiwen Zhu1
  • 1Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
* Co-first authors
Received: March 20, 2020Accepted: June 4, 2020Published: July 26, 2020

Copyright: © 2020 Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Intestinal barrier dysfunction is a hallmark of inflammatory bowel disease (IBD). MiR-155 is increased in colitis and downregulates expression of hypoxia-inducible factor 1α (HIF-1α). Here, we investigated the effects of miR-155 on intestinal barrier dysfunction in dextran sulfate sodium (DSS)-induced colitis. We found that miR-155 antagomir treatment relieved weight loss and intestinal damage in IBD mouse models (P < 0.05). Furthermore, electron microscopy and immunofluorescence imaging showed that miR-155 increased intestinal barrier dysfunction and downregulated the expression of tight junction proteins in DSS-induced colitis. FG-4497, which upregulates HIF-1α expression, elicited protective effects on the intestinal barrier in DSS-induced colitis. Dual luciferase reporter assays also confirmed that miR-155 downregulated expression of HIF-1α. Finally, we discovered that HIF-1α levels were elevated by miR-155 antagomir treatment (P < 0.05) and that TFF-3 expression correlated positively with HIF-1α expression. These results suggest that miR-155 contributes to DSS-induced colitis by promoting intestinal barrier dysfunction and inhibiting the HIF-1α/TFF-3 axis.