Overexpression of miR-21 in patients with ulcerative colitis impairs intestinal epithelial barrier function through targeting the Rho GTPase RhoB

• Published in: Biochemical and biophysical research communications 2013-05, Vol.434 (4), p.746-752
• Main Authors: Yang, Yongzhi, Ma, Yanlei, Shi, Chenzhang, Chen, Hongqi, Zhang, Huizhen, Chen, Niwei, Zhang, Peng, Wang, Feng, Yang, Jun, Yang, Jianjun, Zhu, Qingchao, Liang, Yong, Wu, Wen, Gao, Renyuan, Yang, Zhe, Zou, Yang, Qin, Huanlong
• Format: Article
• Language: English
• Subjects: Adult; Aged; Blotting, Western; Caco-2 Cells; Colitis, Ulcerative - genetics; Colitis, Ulcerative - metabolism; Epithelial Cells - metabolism; Female; Gene Expression; Humans; Immunohistochemistry; In Situ Hybridization; Intestinal epithelial barrier; Intestinal Mucosa - metabolism; Male; MicroRNAs - genetics; MicroRNAs - metabolism; Microscopy, Electron, Transmission; Middle Aged; miR-21; Permeability; Reverse Transcriptase Polymerase Chain Reaction; RhoB; rhoB GTP-Binding Protein - genetics; rhoB GTP-Binding Protein - metabolism; RNA Interference; RNA, Messenger - genetics; RNA, Messenger - metabolism; Tight Junctions - metabolism; Tight Junctions - ultrastructure; Ulcerative colitis; Young Adult
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2013.03.122

•Both the mucosal and serum levels of miR-21 were upregulated in UC.•Overexpression of miR-21 impaired the integrity of the tight junctions.•miR-21 induced the depletion of RhoB and the impairment of the tight junctions. Although epithelial barrier dysfunction in the gut has been extensively reported in ulcerative colitis (UC), the pathogenesis of this disease is not completely understood. In the present study, we investigated the role of miR-21 in regulating intestinal epithelial barrier function in UC. Colonic biopsies were obtained from 30 chronic UC patients and 30 healthy controls. Using real-time quantitative polymerase chain reaction (qRT-PCR), we found that both the mucosal and serum levels of miR-21 were upregulated in UC. In situ hybridization (ISH) analysis confirmed the accumulation of miR-21 in UC epithelia cells in vivo. Immunohistochemistry, Western Blot, qRT-PCR, and ultrastructural analyses further demonstrated that the overexpression of miR-21 in UC mucosa and Caco-2 cells impaired the integrity of the tight junctions, resulted in a decrease of the transepithelial electrical resistance (TER) and an increase of the inulin permeability. Furthermore, miR-21 induced the degradation of RhoB mRNA, which led to the depletion of RhoB and the impairment of tight junctions in intestinal epithelial cells.