microRNA-222 modulates liver fibrosis in a murine model of biliary atresia

Biochem Biophys Res Commun. 2014 Mar 28;446(1):155-9. doi: 10.1016/j.bbrc.2014.02.065. Epub 2014 Feb 22.

Abstract

microRNA-222 (miR-222) has been shown to initiate the activation of hepatic stellate cells, which plays an important role in the pathogenesis of liver fibrosis. The aim of our study was to evaluate the role of miR-22 in a mouse model of biliary atresia (BA) induced by Rhesus Rotavirus (RRV) infection. New-born Balb/c mice were randomized into control and RRV infected groups. The extrahepatic bile ducts were evaluated. The experimental group was divided into BA group and negative group based on histology. The expression of miR-222, protein phosphatase 2 regulatory subunit B alpha (PPP2R2A), proliferating cell nuclear antigen (PCNA) and phospho-Akt were detected. We found that the experimental group showed signs of cholestasis, retardation and extrahepatic biliary atresia. No abnormalities were found in the control group. In the BA group, miR-222, PCNA and Akt were highly expressed, and PPP2R2A expression was significantly inhibited. Our findings suggest that miR-222 profoundly modulated the process of fibrosis in the murine BA model, which might represent a potential target for improving BA prognosis.

Keywords: Biliary atresia; Liver fibrosis; Murine model; microRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Biliary Atresia / etiology*
  • Biliary Atresia / genetics
  • Biliary Atresia / pathology
  • Disease Models, Animal
  • Female
  • Liver / metabolism
  • Liver / pathology
  • Liver Cirrhosis / etiology*
  • Liver Cirrhosis / genetics
  • Liver Cirrhosis / pathology
  • Mice
  • Mice, Inbred BALB C
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism*
  • Pregnancy
  • Proliferating Cell Nuclear Antigen / genetics
  • Proliferating Cell Nuclear Antigen / metabolism
  • Protein Phosphatase 2 / genetics
  • Protein Phosphatase 2 / metabolism
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rotavirus Infections / complications

Substances

  • MIRN222 microRNA, mouse
  • MicroRNAs
  • Proliferating Cell Nuclear Antigen
  • RNA, Messenger
  • Proto-Oncogene Proteins c-akt
  • Ppp2r2a protein, mouse
  • Protein Phosphatase 2