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GSK3β plays pro-fibrogenic activity through TGF-beta/Smad signaling pathway in renal tubular epithelial cells
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- Author:
- No author available
- Journal Title:
- Acta Academiae Medicinae Militaris Tertiae
- Issue:
- 19
- DOI:
- No doi available
- Key Word:
- 肾脏纤维化;糖原合成酶激酶3;转化生长因子β1;Smad3蛋白质
Abstract： 目的 阐明GSKββ对于肾脏小管间质纤维化的作用.方法 以TGF-β1诱导的体外肾小管间质纤维化模型为研究对象,以GSK3β特异抑制剂LiCl处理细胞和不同GSK3β表达质粒(野生型GSK3β表达质粒GSK3β-WT;第9位点上丝氨酸突变为丙氨酸,由此不能再被磷酸化失活而具有固有活性的GSK3β突变质粒GSK3 β-S9A;第85、86位点上赖氨酸突变为丙氨酸、失去激酶活性的GSK3β突变质粒GSK3β-KD)转染细胞,观察肾脏纤维化的标志性分子纤维连接素蛋白(fibronectin,FN)表达水平的改变,以及对TGF- β/Smad信号通路的作用.结果 LiCl增加HK-2细胞GSK3β的磷酸化,抑制GSK3β的活性,同时降低了细胞基础水平和TGF-β1诱导的FN表达.过表达的GSK3β-WT增强TGF-β1诱导的FN表达,而这种效应在GSK3β-S9A转染细胞更为显著.过表达GSK3β-KD抑制TGF-β1诱导的FN表达.分析对TGF-β/Smad信号通路的作用,LiCl可以抑制TGF-β1诱导的Smad3磷酸化,而对Smad2磷酸化水平无影响.同时,LiCl也不改变Smad3的总蛋白表达.结论 GSK3β通过TGF-β1/Smad3信号通路促HK-2细胞纤维化,抑制GSK3β可以抗纤维化.
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