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

被引:185
作者
Yang, Yongzhi [1 ]
Ma, Yanlei [2 ]
Shi, Chenzhang [1 ]
Chen, Hongqi [1 ]
Zhang, Huizhen [3 ]
Chen, Niwei [4 ]
Zhang, Peng [2 ]
Wang, Feng [2 ]
Yang, Jun [1 ]
Yang, Jianjun [1 ]
Zhu, Qingchao [1 ]
Liang, Yong [1 ]
Wu, Wen [1 ]
Gao, Renyuan [1 ]
Yang, Zhe [1 ]
Zou, Yang [1 ]
Qin, Huanlong [2 ]
机构
[1] Shanghai Jiao Tong Univ, Peoples Hosp 6, Dept Surg, 600 Yishan Rd, Shanghai 200233, Peoples R China
[2] Tongji Univ, Shanghai Peoples Hosp 10, Dept Gen Surg, Shanghai 200072, Peoples R China
[3] Shanghai Jiao Tong Univ, Peoples Hosp 6, Dept Pathol, Shanghai 200233, Peoples R China
[4] Shanghai Jiao Tong Univ, Peoples Hosp 6, Dept Gastroenterol, Shanghai 200233, Peoples R China
基金
中国国家自然科学基金;
关键词
Ulcerative colitis; miR-21; Intestinal epithelial barrier; RhoB; INFLAMMATORY-BOWEL-DISEASE; TUMOR-SUPPRESSOR RHOB; CIRCULATING MICRORNA; EXPRESSION; PERMEABILITY; ORGANIZATION; JUNCTIONS; SYSTEM; CELLS;
D O I
10.1016/j.bbrc.2013.03.122
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
070307 [化学生物学]; 071010 [生物化学与分子生物学];
摘要
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. (c) 2013 Elsevier Inc. All rights reserved.
引用
收藏
页码:746 / 752
页数:7
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