Dong Zhao1, Yi Luo1, Yun Xia1, Jian-Jun Zhang1, Qiang Xia2. 1. Department of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Dongfang Rd., No. 1630, Shanghai, 200127, China. 2. Department of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Dongfang Rd., No. 1630, Shanghai, 200127, China. xiaqiang@shsmu.edu.cn.
Abstract
BACKGROUND AND AIM: 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. METHODS: 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 in vitro. RESULTS: 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. In vitro, 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 type I 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 homolog 3 (SMAD3) expression and blocking of TGF-β-induced expression of a1(I) and a2(I) procollagen miRNAs. CONCLUSIONS: Our data indicate that miR-19b may be involved in BA-related fibrosis.
BACKGROUND AND AIM: 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. METHODS: 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 in vitro. RESULTS: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. In vitro, 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 type I 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 homolog 3 (SMAD3) expression and blocking of TGF-β-induced expression of a1(I) and a2(I) procollagen miRNAs. CONCLUSIONS: Our data indicate that miR-19b may be involved in BA-related fibrosis.
Authors: Bing Q Huang; Tatyana V Masyuk; Melissa A Muff; Pamela S Tietz; Anatoliy I Masyuk; Nicholas F Larusso Journal: Am J Physiol Gastrointest Liver Physiol Date: 2006-09 Impact factor: 4.052
Authors: Ronald J Sokol; Ross W Shepherd; Riccardo Superina; Jorge A Bezerra; Patricia Robuck; Jay H Hoofnagle Journal: Hepatology Date: 2007-08 Impact factor: 17.425