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Digestive Diseases and Sciences

, Volume 60, Issue 7, pp 2038–2048 | Cite as

MicroRNA-370 Attenuates Hepatic Fibrogenesis by Targeting Smoothened

  • Cui-Hua Lu
  • Qian-Ru Hou
  • Long-Fei Deng
  • Chen Fei
  • Wen-Ping Xu
  • Qin Zhang
  • Kai-Ming Wu
  • Bei-Fang Ning
  • Wei-Fen Xie
  • Xin Zhang
Original Article

Abstract

Background and Aims

Recent research shows that abnormal expression of microRNA plays an important role in the process of hepatic fibrosis . miR-370 has been reported to be involved in liver function and is suppressed during hepatic carcinogenesis. The aim of this study was to investigate the role of miR-370 in hepatic fibrosis.

Methods

The expression levels of miR-370 in rat fibrotic livers and activated hepatic stellate cells (HSCs) were evaluated by quantitative real-time PCR. The effect of miR-370 on the activation of HSCs was analyzed by flow cytometric analyses, real-time PCR and Western blot. Adenovirus carrying miR-370 was injected through the tail vein to access the effect of miR-370 on hepatic fibrosis induced by CCl4 in rats. The downstream targets of miR-370 were predicted by the Target Scan database and verified by luciferase assays, real-time PCR and Western blot in HSCs and were further confirmed by immunohistochemistry in vivo.

Results

Real-time PCR showed that miR-370 expression was significantly reduced in rat fibrotic livers and TGFβ1-stimulated HSCs. Overexpression of miR-370 inhibited the proliferation of HSC-T6 cells via inducing cell apoptosis and suppressed the activation of HSCs. Upregulation of miR-370 obviously attenuated the CCl4-induced liver fibrosis in rats. miR-370 was directly bound to the 3′UTR of Smoothened (SMO) and suppressed the expression of SMO in HSCs and fibrotic livers.

Conclusions

Our study demonstrated that miR-370 plays an inhibitory role in hepatic fibrogenesis by targeting SMO. Restoration of miR-370 may have beneficial effects on the treatment of liver fibrosis.

Keywords

miR-370 Hepatic fibrosis Smoothened Hedgehog signal 

Notes

Acknowledgments

This work was supported by the National Natural Science Foundation of China (81372675), Shanghai Science and Technology Committee for Key Projects (13JC1407401) and Foundation for Talents in Six Fields of Jiangsu Province (no. 2011-WS- 061).

Conflict of interest

None.

Supplementary material

10620_2015_3585_MOESM1_ESM.docx (13 kb)
Supplementary material 1 (DOCX 12 kb)
10620_2015_3585_MOESM2_ESM.docx (331 kb)
Supplementary material 2 (DOCX 330 kb)

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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Cui-Hua Lu
    • 1
  • Qian-Ru Hou
    • 1
  • Long-Fei Deng
    • 2
  • Chen Fei
    • 2
  • Wen-Ping Xu
    • 2
  • Qin Zhang
    • 2
  • Kai-Ming Wu
    • 2
  • Bei-Fang Ning
    • 2
  • Wei-Fen Xie
    • 2
  • Xin Zhang
    • 2
  1. 1.Department of Gastroenterology, Affiliated Hospital of Nantong UniversityMedical College of Nantong UniversityNantongChina
  2. 2.Department of Gastroenterology, Changzheng HospitalSecond Military Medical UniversityShanghaiChina

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