PT  - JOURNAL ARTICLE
AU  - Chong He
AU  - Yan Shi
AU  - Ruijin Wu
AU  - Mingming Sun
AU  - Leilei Fang
AU  - Wei Wu
AU  - Changqin Liu
AU  - Maochun Tang
AU  - Zhong Li
AU  - Ping Wang
AU  - Yingzi Cong
AU  - Zhanju Liu
TI  - miR-301a promotes intestinal mucosal inflammation through induction of IL-17A and TNF-α in IBD
AID  - 10.1136/gutjnl-2015-309389
DP  - 2016 Dec 01
TA  - Gut
PG  - 1938--1950
VI  - 65
IP  - 12
4099  - http://gut.bmj.com/content/65/12/1938.short
4100  - http://gut.bmj.com/content/65/12/1938.full
SO  - Gut2016 Dec 01; 65
AB  - Objective MicroRNA (miR)-301a is known to be involved in the tumourigenesis and pathogenesis of several autoimmune diseases, but it remains unclear whether miR-301a is associated with the pathogenesis of IBD.Methods miR-301a expression was assessed in peripheral blood mononuclear cells (PBMC) and inflamed mucosa of patients with IBD by quantitative real-time-PCR. Peripheral blood CD4+ T cells were transduced with lentivirus-encoding pre-miR-301a (LV-miR-301a) or a reverse complementary sequence of miR-301a (LV-anti-miR-301a), and their differentiation and activation were investigated in vitro. Antisense miR-301a was administered into mice during trinitrobenzene sulphonic acid (TNBS)-induced colitis to determine its role in colitis.Results miR-301a expression was significantly upregulated in PBMC and inflamed mucosa of patients with IBD compared with healthy controls. Stimulation with tumour necrosis factor-α (TNF-α) significantly enhanced miR-301a expression in IBD CD4+ T cells, which was markedly reversed by anti-TNF-α mAb (Infliximab) treatment. Transduction of LV-miR-301a into CD4+ T cells from patients with IBD promoted the Th17 cell differentiation and TNF-α production compared with the cells with expression of LV-anti-miR-301a. SNIP1 as a functional target of miR-301a was reduced in miR-301a expression but increased in LV-anti-miR-301a expression. Knockdown of SNIP1 could enhance Th17 cell differentiation. Furthermore, intracolonical administration of antisense miR-301a in TNBS-induced mouse colitis model significantly decreased numbers of interleukin (IL)-17A+ cells and amounts of pro-inflammatory cytokines (eg, IL-17A, TNF-α) in inflamed colon.Conclusions Our data reveal a novel mechanism in which the elevated miR-301a in PBMC and inflamed mucosa of IBD promotes Th17 cell differentiation through downregulation of SNIP1. Blockade of miR-301a in vivo may serve as a novel therapeutic approach in the treatment of IBD.