RT Journal Article
SR Electronic
T1 miR-301a promotes intestinal mucosal inflammation through induction of IL-17A and TNF-α in IBD
JF Gut
JO Gut
FD BMJ Publishing Group Ltd and British Society of Gastroenterology
SP 1938
OP 1950
DO 10.1136/gutjnl-2015-309389
VO 65
IS 12
A1 He, Chong
A1 Shi, Yan
A1 Wu, Ruijin
A1 Sun, Mingming
A1 Fang, Leilei
A1 Wu, Wei
A1 Liu, Changqin
A1 Tang, Maochun
A1 Li, Zhong
A1 Wang, Ping
A1 Cong, Yingzi
A1 Liu, Zhanju
YR 2016
UL http://gut.bmj.com/content/65/12/1938.abstract
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.