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

Abstract

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.

Serum TGF-β1 and VEGF Levels Reflect the Liver Hardness and Function in Children with Biliary Atresia

“…However, due to the occurrence of progressive liver fibrosis, cholestatic cirrhosis, and portal hypertension, most children must choose liver transplantation. Progressive liver fibrosis is a major constraint on Kasai's surgical results which show that in cervical, preventing the progression of liver fibrosis will significantly improve the outcome of Kasai surgery, and the transforming growth factor- β 1 (TGF- β 1) protein regulates cell growth [ 18 ].…”

Biliary Atresia: A Complex Hepatobiliary Disease with Variable Gene Involvement, Diagnostic Procedures, and Prognosis

“…Thus, far from being univocal, the genetic research on biliary atresia revealed that other genes involved in biliary tract dysmorphogenesis and cholestasis, the immunologic response, vasculogenesis, and left-right patterning might contribute to this disease with worrisome complications and prognosis. Currently, clinical investigations and nonhuman model systems orientate also on CFC1 , CFTR , JAG1 , IFN-γ , INV , MIF , VEGF , SOX17 , and ZIC3 [ 6 , 33 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 ].…”