Effect of microRNA-155 on the Interferon- Gamma Signaling Pathway in Biliary Atresia

Yu-An Hsu ； Chih-Hung Lin ； Hui-Ju Lin ； Chi-Chun Huang ； Hsiu-Chu Lin ； Ying-Chi Chen ； Ching-Yao Chang ； Su-Hua Huang ； Jane-Ming Lin ； Kuan-Rong Lee ； Lei Wan

《The Chinese Journal of Physiology》 59卷6期 (2016/12) Pp. 315-322

https://doi.org/10.4077/CJP.2016.BAE419

摘要

MicroRNAs (miRNAs) are ~22-nucleotide long RNAs that negatively regulate gene expression and inflammatory responses in eukaryotes. The aim of this work was to evaluate the roles of miRNA (miR)-155 on the interferon-γ (IFN-γ)-induced response in biliary atresia (BA), which is the most common form of pediatric chronic liver disease and a leading indication for pediatric liver transplantation. The expression of miR-155 and the suppressor of cytokine signaling 1 (SOCS1) gene in human and mice liver tissues of BA and healthy controls was evaluated. IFN-γ-induced expression of miR-155, inflammatory cytokines and chemokines was determined in bile duct cells. A miR-155 inhibitor was used to determine the influence in the IFN-γ-induced signaling pathway by western blot analysis. A strong up-regulation of miR-155 expression was observed in BA histologic sections and mouse bile duct cells treated with IFN-γ. miR-155 down-regulated SOCS1 protein expression by targeting its mRNA. Up-regulation of miR-155 expression by IFN-γ in bile duct cells led to the activation of signal transducers and activators of transcription 1 (Stat1) and inflammatory cytokines through the Janus kinase (Jak)/Stat pathway, whereas targeted inhibition of miR-155 expression by anti-miRNA oligonucleotides significantly decreased the mRNA or protein expression levels of these inflammatory cytokines and Stat1. Overall, our results suggest that miR-155 regulates the IFN-γ signaling pathway by targeting SOCS1 expression and may be a potential target in BA therapy

關鍵字

bile duct ； inflammatory response ； interferon gamma ； Jak/Stat pathway ； microRNA-155 ； SOCS1

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