Long non-coding RNA APTR promotes the activation of hepatic stellate cells and the progression of liver fibrosis

Biochem Biophys Res Commun. 2015 Aug 7;463(4):679-85. doi: 10.1016/j.bbrc.2015.05.124. Epub 2015 Jun 1.

Abstract

In this study, we aimed at assessing a role of Alu-mediated p21 transcriptional regulator (APTR) in hepatofibrogenesis. APTR was upregulated in fibrotic liver samples and activated hepatic stellate cells (HSCs). Knockdown of APTR inhibited the activation of HSCs in vitro and mitigated the accumulation of collagen in vivo. Importantly, APTR silencing could abrogate TGF-β1-induced upregulation of α-SMA in HSCs. In addition, inhibition of cell cycle and cell proliferation by APTR knockdown was attenuated by p21 siRNA1 in primary HSCs. Finally, serum APTR levels were increased in patients with liver cirrhosis, indicating a potential biomarker for liver cirrhosis. Collectively, evidence is proposed for a new biological role of APTR in hepatofibrogenesis.

Keywords: Alu-mediated p21 transcriptional regulator; Hepatic stellate cells; Liver fibrosis; Long non-coding RNA; p21.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Proliferation
  • Disease Progression
  • Gene Knockdown Techniques
  • Gene Silencing
  • Hepatic Stellate Cells / physiology*
  • Liver Cirrhosis / blood
  • Liver Cirrhosis / pathology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • RNA, Long Noncoding / blood
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / physiology*
  • Real-Time Polymerase Chain Reaction

Substances

  • RNA, Long Noncoding