Down-regulation of circDMNT3B is conducive to intestinal mucosal permeability dysfunction of rats with sepsis via sponging miR-20b-5p.

Jiao Liu, Yongan Liu, Lidi Zhang, Yizhu Chen, Hangxiang Du, Zhenliang Wen, Tao Wang, Dechang Chen

Journal of cellular and molecular medicine 2020 Jun

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Sepsis is a life-threatening syndrome with a high risk of mortality, which is caused by the dysregulated host response to infection. We examined significant roles of circDMNT3B and miR-20b-5p in the intestinal mucosal permeability dysfunction of rats with sepsis. SD rats were randomly divided into 6 groups (n = 10/group): sham group, sepsis group, si-negative control group, circDNMT3B-si1 group, circDNMT3B-si2 group and circDNMT3B-si1 + anti-miR-20b-5p group. The level of malondialdehyde (MDA) content, superoxide dismutase (SOD) activity, interleukin (IL)-6 and IL-10 levels were measured through ELISA assay kits. Cell survival rate and cell apoptosis were evaluated by Cell-Counting Kit-8 Assay and flow cytometry, respectively. Luciferase reporter assays were used to investigate interactions between miR-20b-5p circDMNT3B in HEK-293T cells. Silencing circDNMT3B can significantly increase the level of d-lactic acid, FD-40, MDA, diamine oxidase, IL-10 and IL-6, compared with sepsis group, while the SOD activity was lower. Silencing circDNMT3B leads to oxidative damage and influence inflammatory factors level in intestinal tissue. CircDNMT3B was identified as a target gene of miR-20b-5p. Silencing circDNMT3B decreased cell survival and induced apoptosis in Caco2 cells treated with LPS, which was reversed by anti-miR-20b-5p. MiR-20b-5p inhibitor remarkably down-regulated mentioned-above levels, in addition to up-regulate SOD activity, which may relieve the damage of intestinal mucosal permeability caused by silencing circDNMT3B in sepsis rats. Down-regulation of circDMNT3B was conducive to the dysfunction of intestinal mucosal permeability via sponging miR-20b-5p in sepsis rats, which may provide the novel strategy for sepsis treatment in the future. © 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.

Citation

Jiao Liu, Yongan Liu, Lidi Zhang, Yizhu Chen, Hangxiang Du, Zhenliang Wen, Tao Wang, Dechang Chen. Down-regulation of circDMNT3B is conducive to intestinal mucosal permeability dysfunction of rats with sepsis via sponging miR-20b-5p. Journal of cellular and molecular medicine. 2020 Jun;24(12):6731-6740