基于Hippo/YAP通路探讨红花总黄酮对肝星状细胞活化增殖的作用机制研究
Exploring the effects of total flavonoids from Carthamus tinctorius L on hepatic stellate cells based on the Hippo/YAP pathway
摘要
Abstract
Objective:To study the effect and mechanism of total saffron flavonoids(TFCTL)on the activation and prolifera-tion of hepatic stellate cells.Methods:HSC-T6 cells in logarithmic growth phase were cultured,and their activation was induced by stimulation with 10 ng/mL of TGF-β1,which were divided into the blank group,TGF-β group,TFCTL low-concentration group(20 μg/mL),TFCTL-medium-concentration group(40 μg/mL),and TFCTL-high-concentration group(60 μg/mL);the CCK-8 kit and apoptosis kit were applied to detect the proliferative activity and apoptosis rate of HSC-T6 cells after the inter-vention of safflower total flavonoids;immunofluorescence staining method was used to observe the expression and position of α-SMA and YAP in the cells of each group;RT-qPCR was used to detect the expression levels of mRNA of α-SMA,CollagenⅠ,MST1,LATS1 and YAP,and Western blot was used to detect the expression levels of α-SMA,CollagenⅠ,MST1,LATS1,and p-YAP/YAP protein expression.Results:Total flavonoids of safflower significantly inhibited the proliferation and promoted the apoptosis of activated HSC-T6 cells.RT-qPCR and Western blot assays revealed that α-SMA,CollagenⅠ,and YAP mRNA levels and protein expression were significantly increased in the TGF-β group compared with the blank group(P<0.01),and the levels of MST1,LATS1 mRNA levels and protein expression were significantly reduced(P<0.05);compared with the TGF-β group,α-SMA,CollagenⅠ,YAP mRNA levels and protein expression were significantly reduced(P<0.01),and MST1,LATS1 mRNA levels and protein expression were significantly increased(P<0.01)in the TFCTL low-,medium-,and high-concentration groups;quantitative immunofluorescence experiments showed that after TFCTL intervention,the fluores-cence intensity of α-SMA in HSC-T6 cells was gradually reduced and the nuclear translocation of YAP was promoted.Conclu-sion:TFCTL may inhibit the activation and proliferation of hepatic stellate cells by suppressing the expression of kinases at all lev-els of the Hippo/YAP pathway,and then attenuate liver fibrosis.关键词
肝纤维化/肝星状细胞/红花总黄酮/Hippo/YAP通路/HSC-T6细胞Key words
Liver fibrosis/Hepatic stellate cells/Carthamus tinctorius L of total flavonoids/Hippo/YAP pathway/HSC-T6 Cells分类
医药卫生引用本文复制引用
赵晓璐,李明奇,王映荷,马月宏..基于Hippo/YAP通路探讨红花总黄酮对肝星状细胞活化增殖的作用机制研究[J].海南医科大学学报,2025,31(12):909-915,7.基金项目
This study was supported by National Natural Science Foundation of China(82460819,81960759,81560706) （82460819,81960759,81560706）
Natural Science Foundation of Inner Mongolia Autonomous Region(2024LHM08029,2019MS08010) （2024LHM08029,2019MS08010）
Inner Mongolia Autonomous Region Grassland Talent Training Program （）
Zhiyuan Talent Project of Inner Mongolia Medical University(ZY20241201) （ZY20241201）
Inner Mongolia Talent Development Fund(22056) （22056）
Key Project of Inner Mongolia Medical University(YKD2022ZD019) （YKD2022ZD019）
Technology Innovation Team for Research on the Anti Liver Fibrosis Effect of Mongolian Medicine at Inner Mongolia Medical University(YKD2022TD039) 国家自然科学基金资助项目(82460819,81960759,81560706) （YKD2022TD039）
内蒙古自治区自然科学基金(2024LHMS08029,2019MS08010) （2024LHMS08029,2019MS08010）
内蒙古自治区草原英才培养计划 （）
内蒙古医科大学致远人才项目治学人才(ZY20241201) （ZY20241201）
内蒙古人才开发基金(22056) （22056）
内蒙古医科大学重点项目(YKD2022ZD019) （YKD2022ZD019）
内蒙古医科大学蒙药抗肝纤维化作用研究科技创新团队(YKD2022TD039) （YKD2022TD039）
