title: Adipose-Derived Mesenchymal Stem Cells Ameliorate Ulcerative Colitis Through miR-1236 Negatively Regulating the Expression of Retinoid-Related Orphan Receptor Gamma.
abstract: Mesenchymal stem cells (MSCs) were reported to accelerate the curing of ulcerative colitis (UC). Altered expression of microRNAs (miRNAs) has recently revealed association with UC. However, the effect of adipose-derived MSCs (ASCs) on UC and the mechanism of how miRNAs regulate UC remain unclear. We investigated the effect of ASCs on 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced UC in rat colon tissues. qRT-PCR and immunofluorescence analyses were performed to monitor the expression of miR-1236 and its target molecule, retinoid-related orphan receptor γ (RORγ). Regulation of the expression of RORγ by miR-1236 was assessed using luciferase reporter construct assays and miR-1236 mimic transfection. The relationship between miR-1236 and RORγ was further investigated in HT29 cells induced by TNF-α. ASCs highly ameliorated UC and decreased the inflammation markers in rats with TNBS-induced UC. In addition, ASCs upregulated the expression of miR-1236 and decreased the expression of RORγ in the TNBS-induced rat model of UC. The luciferase reporter assay and bioinformatic analysis demonstrated that the expression of RORγ was directly targeted and regulated by miR-1236. Specifically, the expression of RORγ was suppressed by miR-1236 mimic and enhanced by miR-1236 inhibitor. Furthermore, we demonstrated that exogenous miR-1236 mimic could inhibit the expression of RORγ in HT29 cell induced by TNF-α. ASCs effectively alleviated UC in rats with the expression of miR-1236 alteration, and miR-1236 may play important roles in UC by downregulating the expression of RORγ.
authors.affiliation: Second Department of Gastroenterology, The Shengjing Affiliated Hospital, China Medical University , Shenyang, Liaoning, People's Republic of China .
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Second Department of Gastroenterology, The Shengjing Affiliated Hospital, China Medical University , Shenyang, Liaoning, People's Republic of China .
authors.forename: Yu
authors.initials: Y
authors.lastname: Jin
authors.affiliation: Second Department of Gastroenterology, The Shengjing Affiliated Hospital, China Medical University , Shenyang, Liaoning, People's Republic of China .
authors.forename: Yan
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Second Department of Gastroenterology, The Shengjing Affiliated Hospital, China Medical University , Shenyang, Liaoning, People's Republic of China .
authors.forename: Lian-jie
authors.initials: LJ
authors.lastname: Lin
authors.affiliation: Second Department of Gastroenterology, The Shengjing Affiliated Hospital, China Medical University , Shenyang, Liaoning, People's Republic of China .
authors.forename: Yong
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Second Department of Gastroenterology, The Shengjing Affiliated Hospital, China Medical University , Shenyang, Liaoning, People's Republic of China .
authors.forename: Dong-xu
authors.initials: DX
authors.lastname: Wang
authors.affiliation: Second Department of Gastroenterology, The Shengjing Affiliated Hospital, China Medical University , Shenyang, Liaoning, People's Republic of China .
authors.forename: Chang-qing
authors.initials: CQ
authors.lastname: Zheng
mesh_terms: D020413:3' Untranslated Regions; D000273:Adipose Tissue / Q000166:cytology; D000818:Animals; D002478:Cells, Cultured; D003093:Colitis, Ulcerative / Q000139:chemically induced / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D007275:Injections, Intravenous; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000502:physiology; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000235:genetics* / Q000378:metabolism; D017208:Rats, Wistar; D014302:Trinitrobenzenesulfonic Acid / Q000633:toxicity; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D020413:3' Untranslated Regions; C000606811:MIRN-1236 microRNA, rat; D035683:MicroRNAs; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; C539902:Rorc protein, rat; D014409:Tumor Necrosis Factor-alpha; D014302:Trinitrobenzenesulfonic Acid