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MicroRNA-378 limits activation of hepatic stellate cells and liver fibrosis by suppressing Gli3 expression

Author

Listed:
  • Jeongeun Hyun

    (College of Natural Science, Pusan National University)

  • Sihyung Wang

    (College of Natural Science, Pusan National University)

  • Jieun Kim

    (College of Natural Science, Pusan National University)

  • Kummara Madhusudana Rao

    (College of Engineering, Pusan National University)

  • Soo Yong Park

    (College of Engineering, Pusan National University)

  • Ildoo Chung

    (College of Engineering, Pusan National University)

  • Chang-Sik Ha

    (College of Engineering, Pusan National University)

  • Sang-Woo Kim

    (College of Natural Science, Pusan National University
    College of Natural Science, Pusan National University, 63-2 Pusandaehak-ro, Kumjeong-gu, Pusan 46241, Korea)

  • Yang H. Yun

    (College of Engineering, The University of Akron)

  • Youngmi Jung

    (College of Natural Science, Pusan National University
    College of Natural Science, Pusan National University, 63-2 Pusandaehak-ro, Kumjeong-gu, Pusan 46241, Korea)

Abstract

Hedgehog (Hh) signalling regulates hepatic fibrogenesis. MicroRNAs (miRNAs) mediate various cellular processes; however, their role in liver fibrosis is unclear. Here we investigate regulation of miRNAs in chronically damaged fibrotic liver. MiRNA profiling shows that expression of miR-378 family members (miR-378a-3p, miR-378b and miR-378d) declines in carbon tetrachloride (CCl4)-treated compared with corn-oil-treated mice. Overexpression of miR-378a-3p, directly targeting Gli3 in activated hepatic stellate cells (HSCs), reduces expression of Gli3 and profibrotic genes but induces gfap, the inactivation marker of HSCs, in CCl4-treated liver. Smo blocks transcriptional expression of miR-378a-3p by activating the p65 subunit of nuclear factor-κB (NF-κB). The hepatic level of miR-378a-3p is inversely correlated with the expression of Gli3 in tumour and non-tumour tissues in human hepatocellular carcinoma. Our results demonstrate that miR-378a-3p suppresses activation of HSCs by targeting Gli3 and its expression is regulated by Smo-dependent NF-κB signalling, suggesting miR-378a-3p has therapeutic potential for liver fibrosis.

Suggested Citation

  • Jeongeun Hyun & Sihyung Wang & Jieun Kim & Kummara Madhusudana Rao & Soo Yong Park & Ildoo Chung & Chang-Sik Ha & Sang-Woo Kim & Yang H. Yun & Youngmi Jung, 2016. "MicroRNA-378 limits activation of hepatic stellate cells and liver fibrosis by suppressing Gli3 expression," Nature Communications, Nature, vol. 7(1), pages 1-16, April.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms10993
    DOI: 10.1038/ncomms10993
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