MicroRNA-193a-3p Reduces Intestinal Inflammation in Response to Microbiota via Down-regulation of Colonic PepT1.
Intestinal inflammation is characterized by epithelial disruption, leading to the loss of barrier function, recruitment of immune cells, and host immune responses to gut microbiota. PepT1, a di/tripeptide transporter that uptakes bacterial products, is up-regulated in inflamed colon tissue, which implies its role in bacterium-associated intestinal inflammation. Although microRNA (miRNA)-mediated gene regulation has been found to be involved in various processes of inflammatory bowel disease (IBD), the biological function of miRNAs in the pathogenesis of IBD remains to be explored. In this study we detected miRNA expression patterns in colon tissues during colitis and investigated the mechanism underlying the regulation of colonic PepT1 by miRNAs. We observed an inverse correlation between PepT1 and miR-193a-3p in inflamed colon tissues with active ulcerative colitis, and we further demonstrated that miR-193a-3p reduced PepT1 expression and activity as a target gene and subsequently suppressed the NF-κB pathway. Intracolonic delivery of miR-193a-3p significantly ameliorated dextran sodium sulfate-induced colitis, whereas the overexpression of colonic PepT1 via PepT1 3'-untranslated region mutant lentivirus vector abolished the anti-inflammatory effect of miR-193a-3p. Furthermore, antibiotic treatment eliminated the difference in the dextran sodium sulfate-induced inflammation between the presence and absence of miR-193a-3p. These findings suggest that miR-193a-3p regulation of PepT1 mediates the uptake of bacterial products and is a potent mechanism during the colonic inflammation process. Overall, we believe miR-193a-3p may be a potent regulator of colonic PepT1 for maintaining intestinal homeostasis.
From the Department of Gastroenterology, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, 197 Ruijin Second Road, Shanghai 200025, China and.
Xin
X
Dai
Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Hankou Road, Nanjing, Jiangsu 210093, China.
Xi
X
Chen
Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Hankou Road, Nanjing, Jiangsu 210093, China.
Qun
Q
Chen
Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Hankou Road, Nanjing, Jiangsu 210093, China.
Lei
L
Shi
Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Hankou Road, Nanjing, Jiangsu 210093, China.
Hongwei
H
Liang
Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Hankou Road, Nanjing, Jiangsu 210093, China.
Zhen
Z
Zhou
From the Department of Gastroenterology, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, 197 Ruijin Second Road, Shanghai 200025, China and.
Qian
Q
Liu
From the Department of Gastroenterology, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, 197 Ruijin Second Road, Shanghai 200025, China and.
Wenjing
W
Pang
Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Hankou Road, Nanjing, Jiangsu 210093, China.
Dongxia
D
Hou
Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Hankou Road, Nanjing, Jiangsu 210093, China.
Cheng
C
Wang
Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Hankou Road, Nanjing, Jiangsu 210093, China.
Ke
K
Zen
From the Department of Gastroenterology, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, 197 Ruijin Second Road, Shanghai 200025, China and yyz28@medmail.com.cn.
Yaozong
Y
Yuan
Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Hankou Road, Nanjing, Jiangsu 210093, China cyzhang@nju.edu.cn.
Chen-Yu
CY
Zhang
From the Department of Gastroenterology, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, 197 Ruijin Second Road, Shanghai 200025, China and xialu@medmail.com.cn.
Lu
L
Xia
D000818:Animals; D003092:Colitis / Q000235:genetics / Q000276:immunology* / Q000382:microbiology; D003106:Colon / Q000276:immunology*; D015536:Down-Regulation; D005260:Female; D006801:Humans; D007422:Intestines / Q000276:immunology* / Q000382:microbiology; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics / Q000276:immunology*; D064307:Microbiota; D000074011:Peptide Transporter 1; D027981:Symporters / Q000235:genetics* / Q000276:immunology
C546818:MIRN193 microRNA, human; C568257:MIRN193 microRNA, mouse; D035683:MicroRNAs; D000074011:Peptide Transporter 1; C082186:SLC15A1 protein, human; C489941:Slc15a1 protein, mouse; D027981:Symporters
gene regulation; inflammatory bowel disease (IBD); microRNA (miRNA); mucosal immunology; peptide transport