Effect of microRNA-155 on the interferon-gamma signaling pathway in biliary atresia.
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.
Institute of Molecular Medicine, National Tsing Hua University, Hsinchu 30013, Republic of China.
Yu-An
YA
Hsu
Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung 80756, Republic of China.
Chih-Hung
CH
Lin
School of Chinese Medicine, China Medical University, Taichung 40402, Republic of China.|Department of Ophthalmology, China Medical University Hospital, Taichung 40402, Republic of China.
Hui-Ju
HJ
Lin
Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Republic of China.
Chi-Chun
CC
Huang
School of Chinese Medicine, China Medical University, Taichung 40402, Republic of China.|Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Republic of China.
Hsiu-Chu
HC
Lin
School of Chinese Medicine, China Medical University, Taichung 40402, Republic of China.|Department of Biotechnology, Asia University, Taichung 41354, Republic of China.
Ying-Chi
YC
Chen
Department of Biotechnology, Asia University, Taichung 41354, Republic of China.
Ching-Yao
CY
Chang
Department of Biotechnology, Asia University, Taichung 41354, Republic of China.
Su-Hua
SH
Huang
Department of Ophthalmology, China Medical University Hospital, Taichung 40402, Republic of China.
Jane-Ming
JM
Lin
Institute of Molecular Medicine, National Tsing Hua University, Hsinchu 30013, Republic of China.
Kuan-Rong
KR
Lee
School of Chinese Medicine, China Medical University, Taichung 40402, Republic of China.|Department of Biotechnology, Asia University, Taichung 41354, Republic of China.|Department of Gynecology, China Medical University Hospital, Taichung 40402, Republic of China.
Lei
L
Wan
D000818:Animals; D001656:Biliary Atresia / Q000378:metabolism*; D016022:Case-Control Studies; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000378:metabolism*; D015398:Signal Transduction; D000071222:Suppressor of Cytokine Signaling 1 Protein / Q000378:metabolism; D015854:Up-Regulation
D016207:Cytokines; C524942:MIRN155 microRNA, human; D035683:MicroRNAs; C532623:Mirn155 microRNA, mouse; C108944:SOCS1 protein, human; C491590:Socs1 protein, mouse; D000071222:Suppressor of Cytokine Signaling 1 Protein; D007371:Interferon-gamma
bile duct; inflammatory response; interferon gamma; Jak/Stat pathway; microRNA-155; SOCS1