Microcystin-leucine-arginine induces liver fibrosis by activating the Hedgehog pathway in hepatic stellate cells

Shen Gu, Minghao Yan, Cong Wang, Xiannan Meng, Zou Xiang, Yudong Qiu, Xiaodong Han

Research output: Journal article publicationJournal articleAcademic researchpeer-review

3 Citations (Scopus)

Abstract

Microcystin-leucine-arginine (MC-LR), produced by cyanobacteria, accumulates in the liver through blood circulation. We investigated the impact of MC-LR on liver fibrosis. Mice received a daily injection of MC-LR at various concentrations for 14 consecutive days aa and then mouse liver was obtained for histopathological and immunoblot analysis. Next, a human hepatic stellate cell line (LX-2) was treated with MC-LR at various concentrations followed by measurement of cell viability, cell cycle and relevant protein expression levels. Our data confirmed the induction of mouse liver fibrosis after exposure to MC-LR at 15 μg/kg and 30 μg/kg. Furthermore, we demonstrated that LX-2 cells could uptake MC-LR, resulting in cell proliferation and differentiation through impacting the Hedgehog signaling after the treatment of MC-LR at 50 nM. Our data supported that MC- LR could induce liver fibrosis by modulating the expression of the transcription factor Gli2 in the Hedgehog signaling in hepatic stellate cells.

Original languageEnglish
Pages (from-to)770-778
Number of pages9
JournalBiochemical and Biophysical Research Communications
Volume533
Issue number4
Early online date25 Sep 2020
DOIs
Publication statusPublished - 17 Dec 2020
Externally publishedYes

Keywords

  • Gli
  • Liver fibrosis
  • Microcystin-leucine arginine
  • The hedgehog signaling

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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