title: 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 in vitro.
  
  
  
  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.
  
  
  
  Our data indicate that miR-19b may be involved in BA-related fibrosis.
authors.affiliation: Department of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Dongfang Rd., No. 1630, Shanghai, 200127, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Zhao
authors.affiliation: Department of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Dongfang Rd., No. 1630, Shanghai, 200127, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Department of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Dongfang Rd., No. 1630, Shanghai, 200127, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Xia
authors.affiliation: Department of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Dongfang Rd., No. 1630, Shanghai, 200127, China.
authors.forename: Jian-Jun
authors.initials: JJ
authors.lastname: Zhang
authors.affiliation: Department of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Dongfang Rd., No. 1630, Shanghai, 200127, China. xiaqiang@shsmu.edu.cn.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Xia
mesh_terms: D020413:3' Untranslated Regions; D000199:Actins / Q000378:metabolism*; D001656:Biliary Atresia / Q000150:complications / Q000235:genetics / Q000473:pathology; D049109:Cell Proliferation / Q000235:genetics; D002478:Cells, Cultured; D024042:Collagen Type I / Q000378:metabolism*; D015536:Down-Regulation / Q000235:genetics; D055166:Hepatic Stellate Cells / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007223:Infant; D008099:Liver / Q000473:pathology; D008103:Liver Cirrhosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D013223:Statistics as Topic
chemical_list: D020413:3' Untranslated Regions; C541116:ACTA2 protein, human; D000199:Actins; D024042:Collagen Type I; C549214:MIRN19A microRNA, human; D035683:MicroRNAs; D018125:Receptors, Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II
keywords: Biliary atresia; Fibrosis; MicroRNA-19b