MiR-122 regulates collagen production via targeting hepatic stellate cells and suppressing P4HA1 expression

Jiang Li, Mohammed Ghazwani, Yifei Zhang, Jianqin Lu, Jilong Li, Jie Fan, Chandrashekhar R. Gandhi, Song Li

Research output: Contribution to journalArticlepeer-review

139 Scopus citations

Abstract

Background & Aims: MicroRNAs (miRNAs) have been shown to be involved in many biological processes by affecting their target gene expression. miR-122 has been extensively studied in hepatocarcinogenesis. However, the role of miR-122 in liver fibrosis remains unknown. Methods: The mRNA expression levels of miR-122, prolyl 4-hydroxylase subunit alpha-1 (P4HA1), and CCAAT/enhancer binding protein alpha (C/EBPα) were assessed by real-time PCR. The protein expression levels of P4HA1, C/EBPα and collagen, type I, alpha 1 (COL1A1) were analyzed by Western blot and immunofluorescence. MTT assay was used to assess cell proliferation. Chromatin immunoprecipitation (ChIP) assay was used to examine the binding activity of C/EBPα to miR-122 promoter. Results: miR-122 expression was significantly reduced in transactivated HSCs and in the livers of mice treated with CCl4. Overexpression of miR-122 inhibited the proliferation of LX2 cells. We also demonstrated that P4HA1 was a target gene of miR-122. The mRNA expression level of PAHA1 inversely correlated with that of miR-122 in HSCs and in the mouse liver. Overexpression of miR-122 markedly attenuated the expression of P4HA1 via targeting a binding site located at 3′-UTR of P4HA1 mRNA. We further showed that miR-122 overexpression led to decreased collagen maturation and ECM production. Finally, the binding activity of C/EBPα to miR-122 promoter was significantly decreased in activated HSCs. Conclusions: Our study suggests that miR-122 may play an important role in negatively regulating collagen production in HSCs and that targeted expression of miR-122 in HSCs may represent a new strategy for the treatment of liver fibrosis.

Original languageEnglish (US)
Pages (from-to)522-528
Number of pages7
JournalJournal of Hepatology
Volume58
Issue number3
DOIs
StatePublished - Mar 2013
Externally publishedYes

Keywords

  • Collagen maturation
  • HSC
  • Liver fibrosis
  • P4HA1
  • miR-122
  • miRNAs

ASJC Scopus subject areas

  • Hepatology

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