[1]赵凯,陈姗,龚如军,等.GSK3β促进TGF-β1诱导的肾小管上皮HK-2细胞纤维化[J].陆军军医大学学报(原第三军医大学学报),2012,34(19):1921-1924.
 Zhao Kai,Chen Shan,Gong Rujun,et al.GSK3β plays pro-fibrogenic activity through TGF-beta/Smad signaling pathway in renal tubular epithelial cells[J].J Amry Med Univ (J Third Mil Med Univ),2012,34(19):1921-1924.
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陆军军医大学学报(原第三军医大学学报)[ISSN:1000-5404/CN:51-1095/R]

卷:
34卷
期数:
2012年第19期
页码:
1921-1924
栏目:
论著
出版日期:
2012-10-15

文章信息/Info

Title:
GSK3β plays pro-fibrogenic activity through TGF-beta/Smad signaling pathway in renal tubular epithelial cells
作者:
赵凯陈姗龚如军黎松何凤田
第三军医大学基础医学部:生物化学与分子生物学教研室,病原生物学教研室;Division of Kidney Disease and Hypertension, Brown University School of Medicine, Providence, Rhode Island 02903, USA;School of Pharmacy, University of Pittsburgh, Pittsburgh, PA15261,USA
Author(s):
Zhao KaiChen ShanGong RujunLi Song He Fengtian
Department of Biochemistry and Molecular Biology, Department of Pathogenic Biology, College of Basic Medical Sciences, Third Military Medical University, Chongqing, 400038, China;Division of Kidney Disease and Hypertension, Brown University School of Medicine, Providence, Rhode Island 02903, USA; School of Pharmacy, University of Pittsburgh, Pittsburgh, PA15261, USA
关键词:
肾脏纤维化糖原合成酶激酶3转化生长因子β1Smad3蛋白质
Keywords:
renal fibrosis glycogen synthase kinase-3 beta transforming growth factor beta1 Smad3 protein
分类号:
R322.61; R329.26; R394.3
文献标志码:
A
摘要:
目的      阐明GSK3β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GSK3β-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。
Abstract:
Objective       To address whether glycogen synthase kinase-3 beta (GSK3β)plays direct roles in renal fibrosis based on our previous study that expression of GSK3β is substantially increased in transplanted human kidney with chronic allograft nephropathy and valproate markedly ameliorates renal fibrosis in rats with unilateral urethral obstruction.       Methods       A standard in vitro model of interstitial fibrosis, cultured human tubular epithelial (HK-2) cells treated with TGF-β1, was examined in our experiments. A selective GSK3β inhibitor, LiCl was used to suppress the activity of GSK3β. The eukaryotic expression vectors encoding  HA-tagged wild type (WT-GSK3β-HA/pcDNA3.1), uninhibitable mutant GSK3β (S9A-GSK3β-HA/pcDNA3.1) and kinase dead mutant GSK3β (K85,86A-GSK3β-HA/pcDNA3.1) were transfected in HK-2 cells respectively.       Results       LiCl increased the phosphorylation of GSK3β, and suppressed both the basal and TGF-β1 induced fibronectin (FN) expression in HK-2 cells. When transfected with expression vector encoding wild type GSK3β or an mutant GSK3β S9A, HK-2 cells displayed increased FN expression; whereas decreased FN expression was observed when transfected vector encoding GSK3β K85A,K86A. To further analyze the possible pathway that GSK3β regulated fibrosis,it was found that in LiCl treated HK-2 cells,phosphorylation of Smad3 was suppressed. While there was no change observed for the phosphorylation level of Smad2.       Conclusion       In summary,our results suggest that TGF-β/Smad3 pathway can be regulated by GSK3β, and therefore GSK3β plays pro-fibrogenic activity in renal tubular epithelial cells.

相似文献/References:

[1]何其睿,李杨,邓文珍,等.硫氧还蛋白相互作用蛋白通过诱导氧化应激促进肾脏纤维化的发生[J].陆军军医大学学报(原第三军医大学学报),2018,40(22):2061.
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更新日期/Last Update: 2012-09-27