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

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

  • Biochem Biophys Res Commun. 2020 Dec 17;533(4):770-778. doi: 10.1016/j.bbrc.2020.09.075.
Shen Gu 1,  Minghao Yan 2,  Cong Wang 3,  Xiannan Meng 4,  Zou Xiang 5,  Yudong Qiu 6,  Xiaodong Han 7
Affiliations

Affiliations

  • 1 Department of Hepatopancreatobiliary Surgery, Drum Tower Hospital, Medical School of Nanjing University, Zhongshan Road 321, Nanjing, 210008, Jiangsu Province, China; Immunology and Reproduction Biology Laboratory & State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Nanjing, Jiangsu, 210093, China; Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing, Jiangsu, 210093, China. Electronic address: gushen1992@yeah.net.
  • 2 Immunology and Reproduction Biology Laboratory & State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Nanjing, Jiangsu, 210093, China; Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing, Jiangsu, 210093, China. Electronic address: ymh__66@163.com.
  • 3 State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Drug Discovery, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China. Electronic address: wangcongweihai@126.com.
  • 4 Immunology and Reproduction Biology Laboratory & State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Nanjing, Jiangsu, 210093, China; Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing, Jiangsu, 210093, China. Electronic address: mengxiann@yeah.net.
  • 5 Department of Microbiology and Immunology, Mucosal Immunobiology and Vaccine Research Center, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden. Electronic address: xiang.y.zou@polyu.edu.hk.
  • 6 Department of Hepatopancreatobiliary Surgery, Drum Tower Hospital, Medical School of Nanjing University, Zhongshan Road 321, Nanjing, 210008, Jiangsu Province, China. Electronic address: gulou9A@yeah.net.
  • 7 Immunology and Reproduction Biology Laboratory & State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Nanjing, Jiangsu, 210093, China; Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing, Jiangsu, 210093, China. Electronic address: hanxd@nju.edu.cn.
PMID: 32988585 DOI: 10.1016/j.bbrc.2020.09.075
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.

Keywords

Gli; Liver fibrosis; Microcystin-leucine arginine; The hedgehog signaling.

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