Effects of propofol on TGF-β1 induced activation of hepatic  stellate cells and its mechanism

doi:10.12047/j.cjap.5929.2020.060

Abstract

Abstract: Objective: To observe the effects of propofol on the activation of hepatic stellate cell line HSC2-T6 induced by transforming growth factor-beta 1 (TGF-β1) and explore its possible mechanism.Methods: The cells were divided into control group, TGF-β1 group, propofol group, TGF-β1 + propofol group, rapamycin group, TGF-β1 + propofol + rapamycin group. Cells were treated with rapamycin (5 μmol/L) for 1 hour, propofol (100 μmol/L) for 1 hour, then TGF-β1 (5 ng/ml) was added to co-culture for 24 hours. Cell proliferation was measured by MTT assay. The concentrations of hyaluronic acid (HA), collagen IV (IV-C) and laminin (LN) in the supernatant of cell culture medium were measured by ELISA. The ultrastructure of cells was observed by transmission electron microscopy. The expressions of alpha-smooth muscle actin (α-SMA), mammalian rapamycin target protein (mTOR), phosphorylated mTOR (p-mTOR) and the autophagy related gene Beclin 1, LC3 and p62 were measured by Western blot. Results: Compared with control group, cell proliferation, the expression of α-SMA, the concentrations of HA, IV-C and LN in culture supernatant, the number of autophages, the expressions of Beclin-1 and LC3-II, the ratio of LC3-II/LC3-I in HSC2-T6 cells were increased significantly, while the expression of p-mTOR, the ratio of p-mTOR/mTOR and the expression of p62 protein were decreased significantly in TGF-β1 group (All P＜0.05). Compared with TGF-β1 group, cell proliferation, the expression of α-SMA, the concentrations of HA, IV-C and LN in culture supernatant, the number of autophages, the expressions of Beclin-1 and LC3-II, the ratio of LC3-II/LC3-I in HSC2-T6 cells in TGF-β1 group were decreased significantly, and the expression of p-mTOR, the ratio of p-mTOR/mTOR and expression of p62 protein were increased significantly in TGF-β1 + propofol group (All P＜0.05). Conclusion: Propofol inhibits the activation of hepatic stellate cells induced by TGF-beta 1, and its mechanism involves the mTOR-autophagy pathway.

Key words: propofol, transforming growth factor-beta 1, hepatic stellate cells, rapamycin target protein in mammals, autophagy

CLC Number:

R965

ZHANG Qian-lu, KUANG Xin. Effects of propofol on TGF-β1 induced activation of hepatic stellate cells and its mechanism[J]. CJAP, 2020, 36(3): 273-278.

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Effects of propofol on TGF-β1 induced activation of hepatic stellate cells and its mechanism

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