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
- 1 Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
Received: March 20, 2020 Accepted: June 4, 2020 Published: July 26, 2020
https://doi.org/10.18632/aging.103555How to Cite
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.