Dysregulated miR-124 and miR-200 expression contribute to cholangiocyte proliferation in the cholestatic liver by targeting IL-6STAT3 signalling》.pdf

Research Article Dysregulated miR-124 and miR-200 expression contribute to cholangiocyte proliferation in the cholestatic liver by targeting IL-6/STAT3 signalling Yongtao Xiao1,2,3, Jun Wang1,3, Weihui Yan1,3, Ying Zhou1,3, Yingwei Chen2,3, Kejun Zhou2,3, Jie Wen 2,3, Yang Wang2,3, Wei Cai1,2,3,⇑ 1Department of Pediatric Surgery, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; 2Shanghai Institute of Pediatric Research, Shanghai, China; 3Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, China Background Aims: Cholestatic liver disease is associated with Conclusions: Our findings suggest that downregulation of dysregulated expression of microRNAs (miRNAs). However, it miR-124 and upregulation of miR-200 collaboratively promote remains unknown whether miRNAs are involved in the cholesta- bile duct proliferation through the IL-6/STAT3 pathway. sis-induced proliferation of cholangiocytes. In this study, we test- 2014 European Association for the Study of the Liver. Published ed the hypothesis that miRNAs modulate cholangiocyte by Elsevier B.V. All rights reserved. proliferation through effects on the IL-6 pathway, a known regulator of cholangiocyte proliferation. Methods: Expression of IL-6, Foxa2, and phosphorylated signal Introduction transducer activator of transcription 3 (STAT3) was investigated in patients with biliary atresia (BA) and in rats subjected to bile Abnormal cholangiocyte proliferation is a typical feature of duct ligation (BDL). miRNA expression was