Modulation of Wnt/β-catenin signaling pathway by irbesartan in highglucose-induced tubular epithelial-mesenchymal transition
- VernacularTitle:厄贝沙坦对高糖诱导肾小管上皮细胞转分化中Wnt/β-catenin信息途径表达的影响
- Author:
Zhe YAN
;
Fang YAO
;
Liping ZHANG
;
Liqiang LIU
;
Jun HAO
;
Shuxia FU
;
Huijun DUAN
- Publication Type:Journal Article
- Keywords:
Wnt4;
β-catenin;
E-cadherin;
α-SMA;
epithelial-mesenchymal transition;
irbesartan
- From:
Chinese Pharmacological Bulletin
2009;25(12):1630-1634
- CountryChina
- Language:Chinese
-
Abstract:
Aim To investigate the effects of irbesartan on Wnt/β-catenin signaling pathway in tubular epithelial-mesenchymal transition(EMT)in HKCs induced by high-glucose.Methods Human kidney proximal tubular epithelial cell line(HKCs)cultured in vitro was divided into four groups:normal-glucose group,mannitol control group,high-glucose group and high-glucose plus irbesartan group.Immunocytochemistry staining was used to observe the expression of β-catenin;the protein expression of Wnt4,β-catenin,E-cadherin and α-SMA was assessed by Western blot;Wnt4 and β-catenin mRNA were detected by reverse transcription-polymerase chain reaction(RT-PCR).Results Compared with normal-glucose and mannitol control group,both the protein and the mRNA of Wnt4 were up-regulated in HKCs stimulated by high-glucose.α-SMA expression significantly increased but E-cadherin decreased in HG group.The cytoplastic and nuclear fraction of β-catenin enhanced with highglucose stimulation.But no difference of the total protein and mRNA of β-catenin was observed between highglucose-treatment and control groups.Highglucose induced Wnt4 and β-catenin expression in a time-dependent manner,both peaking at 24 h.Irbesartan reduced the promotional effect of HG on Wnt4 and α-SMA expression,and nuclear translocation of β-catenin.HG-mediated inhibition of E-cadherin was also restored by irbesartan.Conclusion These data supported a functional role for Wnt/β-catenin signaling pathway during epithelial-mesenchymal transition of HKCs induced by high glucose and suggested that irbesartan might reverse tubular EMT by regulating activity of Wnt/β-catenin pathway.
