Overexpression of miR-429 impairs intestinal barrier function in diabetic mice by down-regulating occludin expression.
Diabetes mellitus (DM) is a group of metabolic diseases characterised by insulin deficiency/resistance and hyperglycaemia. We previously reported the presence of an impaired tight junction and decreased expression of occludin (Ocln) and zonula occludens-1 (ZO-1) in the intestinal epithelial cells (IECs) of type 1 DM mice, but the exact mechanism remains unclear. In this study, we investigated the role of microRNAs (miRNAs) in impairing the tight junction in IECs of DM mice. Using an integrated comparative miRNA microarray, miR-429 was found to be up-regulated in IECs of type 1 DM mice. Then, miR-429 was confirmed to directly target the 3'-UTR of Ocln, although it did not target ZO-1. Moreover, miR-429 down-regulated the Ocln expression in IEC-6 cells in vitro. Finally, exogenous agomiRNA-429 was shown to down-regulate Ocln and induce intestinal barrier dysfunction in normal mice, while exogenous antagomiRNA-429 up-regulated Ocln in vivo and improved intestinal barrier function in DM mice. In conclusion, increased miR-429 could down-regulate the expression of Ocln by targeting the Ocln 3'-UTR, which impaired intestinal barrier function in DM mice.
Department of Gastroenterology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 107 Yan Jiang Xi Road, Guangzhou, Guangdong, 510120, China.
Tao
T
Yu
Department of Gastroenterology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 107 Yan Jiang Xi Road, Guangzhou, Guangdong, 510120, China.
Xi-Ji
XJ
Lu
Department of Gastroenterology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 107 Yan Jiang Xi Road, Guangzhou, Guangdong, 510120, China.
Jie-Yao
JY
Li
Department of Gastroenterology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 107 Yan Jiang Xi Road, Guangzhou, Guangdong, 510120, China.
Ti-Dong
TD
Shan
Department of Gastroenterology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 107 Yan Jiang Xi Road, Guangzhou, Guangdong, 510120, China.
Can-Ze
CZ
Huang
Department of Gastroenterology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 107 Yan Jiang Xi Road, Guangzhou, Guangdong, 510120, China.
Hui
H
Ouyang
Department of Gastroenterology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 107 Yan Jiang Xi Road, Guangzhou, Guangdong, 510120, China.
Hong-Sheng
HS
Yang
Department of Gastroenterology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 107 Yan Jiang Xi Road, Guangzhou, Guangdong, 510120, China.
Ji-Hao
JH
Xu
Department of Gastroenterology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 107 Yan Jiang Xi Road, Guangzhou, Guangdong, 510120, China.
Wa
W
Zhong
Department of Gastroenterology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 107 Yan Jiang Xi Road, Guangzhou, Guangdong, 510120, China. xiazhongshengsysu@163.com.
Zhong-Sheng
ZS
Xia
Department of Gastroenterology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 107 Yan Jiang Xi Road, Guangzhou, Guangdong, 510120, China. qkchen2015@163.com.
Qi-Kui
QK
Chen
D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D000070416:Antagomirs / Q000378:metabolism; D001483:Base Sequence; D001665:Binding Sites; D002463:Cell Membrane Permeability; D003921:Diabetes Mellitus, Experimental / Q000235:genetics* / Q000473:pathology*; D015536:Down-Regulation / Q000235:genetics; D004847:Epithelial Cells / Q000378:metabolism; D020869:Gene Expression Profiling; D057809:HEK293 Cells; D006801:Humans; D007422:Intestines / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000378:metabolism*; D062793:Occludin / Q000235:genetics* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats
D020413:3' Untranslated Regions; D000070416:Antagomirs; C582202:MIRN429 microRNA, mouse; D035683:MicroRNAs; D062793:Occludin
Diabetes mellitus; Intestinal barrier function; Intestinal epithelial cell; Occludin; miR-429