MicroRNA-19b Expression in Human Biliary Atresia Specimens and Its Role in BA-Related Fibrosis.

Abstract

Biliary atresia (BA) is a pediatric liver disease with unknown underlying etiology. MicroRNAs (miRNAs) represent a family of small noncoding RNAs. Among them, miR-19b has been suggested to function in the diseased liver. We therefore decided to investigate its potential role in BA. We used infant-derived specimens to analyze miR-19b expression in a tissue- and cell-specific fashion, predicted interaction with genes, and finally performed a functional study invitro. Patients with BA showed significantly lower miR-19b level in liver compared with controls, and pediatric end-stage liver disease (PELD) score was inversely correlated with miR-19b level. Invitro, miR-19b was significantly downregulated in activated hepatic stellate cells (HSCs) and exerted inhibitory effects on HSC activation, as confirmed by decreased alpha-smooth muscle actin (α-SMA) and typeI collagen expression. Moreover, one mRNA target gene (TGFβR2) was identified. Computational prediction of miR-19b binding to the 3'-untranslated region (UTR) of TGFβR2 was validated by luciferase reporter assay. Furthermore, miR-19b mimic negatively regulated transforming growth factor-beta (TGF-β) signaling components, as demonstrated by decreased drosophila mothers against decapentaplegic homolog3 (SMAD3) expression and blocking of TGF-β-induced expression of a1(I) and a2(I) procollagen miRNAs. Our data indicate that miR-19b may be involved in BA-related fibrosis.