PICK1在肝纤维化中的表达变化及功能研究 |
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引用本文: | 陈培杰,李俊,黄成,孟晓明,蔡双朋.PICK1在肝纤维化中的表达变化及功能研究[J].安徽医科大学学报,2015(11). |
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作者姓名: | 陈培杰 李俊 黄成 孟晓明 蔡双朋 |
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作者单位: | 安徽医科大学 药学院,合肥 230032;安徽医科大学 肝病研究所,合肥 230032;安徽医科大学 安徽省创新药物产业共性研究院,合肥 230032;安徽医科大学 药学院,合肥 230032;安徽医科大学 肝病研究所,合肥 230032;安徽医科大学 安徽省创新药物产业共性研究院,合肥 230032;安徽医科大学 药学院,合肥 230032;安徽医科大学 肝病研究所,合肥 230032;安徽医科大学 安徽省创新药物产业共性研究院,合肥 230032;安徽医科大学 药学院,合肥 230032;安徽医科大学 肝病研究所,合肥 230032;安徽医科大学 安徽省创新药物产业共性研究院,合肥 230032;安徽医科大学 药学院,合肥 230032;安徽医科大学 肝病研究所,合肥 230032;安徽医科大学 安徽省创新药物产业共性研究院,合肥 230032 |
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基金项目: | 国家自然科学基金(编号81273526、81473268);安徽省重点科技攻关项目(编号1301042212);安徽省自然科学基金(编号1308085MH145);高等学校博士学科点专项科研基金(编号20123420120001) |
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摘 要: | 目的:研究蛋白激酶 C 结合蛋白1(PICK1)在小鼠肝纤维及活化的肝星状细胞中的表达变化,并探讨其对人肝星状细胞株(LX-2)活化的影响。方法建立四氯化碳(CCl4)诱导的小鼠肝纤维化模型,观察 PICK1在肝纤维化过程中的表达变化;转化生长因子β1(TGF-β1)刺激 LX-2活化,West-ern blot 测定 PICK1的蛋白表达情况;转染 PICK1过表达质粒至 LX-2中,再以 TGF-β1诱导活化,Western blot 检测PICK1、α平滑肌肌动蛋白(α-SMA)、I 型胶原(Col1a1)和Smad2、3及其磷酸化水平的蛋白表达情况。结果正常组小鼠肝脏中 PICK1表达较高,随着肝纤维化的加重,PICK1的表达逐渐递减。TGF-β1诱导活化的 LX-2细胞中 PICK1表达降低。转染 PICK1过表达质粒后,TGF-β1诱导的α-SMA、Colla1的表达明显减少,且 Smad2、3磷酸化水平显著下降。结论 PICK1在纤维化肝组织及活化的 HSC 中表达下调。过表达 PICK1可抑制 TGF-β1诱导的 LX-2活化,可能是通过抑制 TGF-β/Smad 通路而发挥作用,为肝纤维化的防治研究提供了新的思路和靶点。
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关 键 词: | PICK1 肝纤维化 肝星状细胞 |
The expression and effect of PICK1 in liver fibrosis |
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Abstract: | Objective To explore the expression of protein interacting with Ca-kinase-1(PICK1)in fibrotic liver of mice and activated hepatic stellate cell,and investigate the effect of PICK1 on the activation of hepatic stellate cell strain (LX-2).Methods Liver fibrosis model in mice was induced by CCl4 and then the PICK1 level was detec-ted in fibrotic liver tissue.LX-2 cells were activated by transforming growth factor β1 (TGF-β1),and the protein level of PICK1 was detected by Western blot.After transfected with the plasmid expressing PICK1,LX-2 was stim-ulated with TGF-β1,the levels of α-smooth muscle actin(α-SMA),collagen type I (Col1a1 ),Smad2,3 and phosphorylation level of them were determined by Western blot.Results PICK1 was highly expressed in normal liver tissues and progressively down-regulated as liver fibrosis progressed.The expression of PICK1 was down-regu-lated in activated LX-2 induced by TGF-β1.The hepatic stellate cell transfected with PICK1-plasmid showed re-markablely decreased TGF-β1-induced α-SMA and Col1a1 expression and obviously declined phosphorylation levels of Smad2 and Smad3.Conclusion The expression of PICK1 decreases in fibrotic livers and activated hepatic stel-late cell.Over-expression of PICK1 can suppress the activation of hepatic stellate cell induced by TGF-β1,and probably because of the inhibitory effect on TGF-β/Smad pathway,which provides new ideas and targets for the prevention and treatment of liver fibrosis. |
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Keywords: | PICK1 Liver Fibrosis hepatic stellate cell |
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