Curcumol alleviates hepatic fibrosis by inducing hepatic stellate cell senescence through Sirt1-p53 signaling pathway
Objective To explore the therapeutic effect of curcumol on hepatic fibrosis and its possible mechanism.Methods Human hepatic stellate cell line HSC-LX2 was cultured with curcumol in different concentrations of 5,10,15,20,30,45,60,80 and 100 μmol/L for 24 hours.The cell viability was detected by CCK-8 method.Three concentrations of curcumol(10,20 and 30 μmol/L)were selected for subsequent experiments.The expressions of α-smooth muscle actin(α-SMA),α1(Ⅰ)collagen and fibronectin were detected by Western blot and immunofluorescence assay.Senescent cells were detected by senescence-associated β-galactosidase(SA-β-Gal)staining.The mRNA expressions of senescence markers p1 6,p21,high mobility group protein A1(HMGA1)and telomerase reverse transcriptase(TERT)were detected by real-time quantitative PCR Western blot was used to detect the protein expressions of silencing mating type information regulator 2 homolog 1(Sirt1)and p53.Results Compared with curcumol 0 μmol/L,curcumol 20 and 30 μmol/L downregulated the expressions of α-SMA,α1(Ⅰ)collagen and fibronectin,increased SA-β-Gal staining positive cells,mRNA expressions of p16,p21 and HMGA1 and protein expression of p53,decreased TERT mRNA expression and Sirt1 protein expression(P<0.05 or P<0.01).The mRNA expressions of p16 and p21 were decreased after adding Sirt1 agonist SRT 1720 5 μmol/L(P<0.01).Conclusion Curcumol could induce hepatic stellate cell senescence through Sirt1-p53 signaling pathway,thereby alleviating hepatic fibrosis.
CurcumolHepatic stellate cellCell senescenceHepatic fibrosisSilencing mating type information regulator 2 homolog 1-p53 signaling pathway