Effect of Berberine on TGF-β1-Induced Proliferation and Activation of Hepatic Stellate Cells by Regulating Hedgehog Signaling Pathway
10.13359/j.cnki.gzxbtcm.2024.08.030
- VernacularTitle:黄连素调节Hedgehog信号通路对TGF-β1诱导的肝星状细胞增殖和活化的影响
- Author:
Lu BAI
1
;
Yi-Lan ZHANG
;
Guang-Yao CHEN
Author Information
1. 河南中医药大学第五临床医学院(郑州人民医院)消化内科,河南郑州 450000
- Keywords:
berberine;
hepatic fibrosis;
TGF-β1;
Hedgehog signaling pathway;
hepatic stellate cells
- From:
Journal of Guangzhou University of Traditional Chinese Medicine
2024;41(8):2145-2152
- CountryChina
- Language:Chinese
-
Abstract:
Objective To observe the effect of berberine on the proliferation and activation of hepatic stellate cells induced by transforming growth factor β1(TGF-β1)via regulating Hedgehog signaling pathway.Methods HSC-T6 cells were cultured and divided into blank group,TGF-β1 group,berberine low-,medium-and high-dose groups,berberine high-dose+purmorphamine(Hedgehog signaling pathway activator)group.After treatment,the proliferation of HSC-T6 cells was detected by methyl thiazolyl tetrazolium(MTT)assay.The apoptosis of HSC-T6 cells was detected by flow cytometry.The expressions of collagen I and α-smooth muscle actin(α-SMA)were detected by immunofluorescence staining.The mRNA expression levels of proliferating cell nuclear antigen(PCNA),Bcl-2 and Bcl-2 associated X protein(Bax)were detected by real-time fluorescence quantitative polymerase chain reaction(qRT-PCR).The protein expression levels of Hedgehog signaling pathway related factors Smo,Gli-1,Shh and Ptch were detected by Western Blot.Results Compared with the blank group,the proliferation rate of HSC-T6 cells,the positive protein expressions of Collagen Ⅰ and α-SMA,the mRNA expression levels of PCNA and Bcl-2,and the protein expression levels of Smo,Gli-1,Shh and Ptch in the TGF-β1 group were significantly increased,while the apoptosis rate and the mRNA expression level of Bax were significantly decreased(all P<0.05).Compared with TGF-β1 group,the proliferation rate of HSC-T6 cells,the expression of Collagen I and α-SMA positive protein,the mRNA expression levels of PCNA and Bcl-2,and the protein expression levels of Smo,Gli-1,Shh and Ptch in berberine low-,medium-and high-dose groups were significantly decreased,while the apoptosis rate and the mRNA expression level of Bax were significantly increased(P<0.05)in a dose-dependent manner.Compared with the high-dose berberine group,the proliferation rate of HSC-T6 cells,the positive proteins expression of Collagen Ⅰ and α-SMA,the mRNA expression levels of PCNA and Bcl-2,and the protein expression levels of Smo,Gli-1,Shh and Ptch in the high-dose berberine+purmorphamine group were significantly increased,while the apoptosis rate and the mRNA expression level of Bax were significantly decreased(all P<0.05).Conclusion Berberine promotes TGF-β1-induced apoptosis of hepatic stellate cells and inhibits their proliferation and activation by regulating Hedgehog signaling pathway.