Role of NOD2-regulated Snail expression in epithelial-mesenchymal transition in podocyte of diabetic nephropathy
10.3760/cma.j.issn.1001-7097.2018.09.006
- VernacularTitle:NOD2调控Snail表达在糖尿病肾病足细胞上皮-间质转分化中的作用
- Author:
Ya ZHANG
1
;
Jin SHANG
;
Luyao WANG
;
Qianxin HE
;
Yanna DOU
;
Dong LIU
;
Genyang CHENG
;
Jing XIAO
;
Zhanzheng ZHAO
Author Information
1. 450052,郑州大学第一附属医院肾内科
- Keywords:
NOD2 Signaling adaptor protein;
Epithelial-mesenchymal transition;
podocyte;
Snail
- From:
Chinese Journal of Nephrology
2018;34(9):673-680
- CountryChina
- Language:Chinese
-
Abstract:
Objective To observe the expression of NOD2 and epithelial-mesenchymal transition (EMT) related proteins in podocytes in high glucose environment,and explore the molecular mechanism of NOD2 involved in EMT.Methods The human glomerular podocytes were the subjects of study.α-SMA and Nephrin expressions were detected by immunofluorescence;the mRNA and protein expressions of NOD2,Snail and EMT related proteins (α-SMA,Desmin,E-cadherin,Nephrin) were detected by real-time fluorescence quantitative PCR and Western blotting.The podocytes were stimulated by high-glucose after shRNA interfering the of NOD2 expression,and the expressions of Snail and subsequent EMT-related proteins were detected by Western blotting.Prior to the activation of NOD2 by muramyl dipeptide (MDP),shRNA was used to interfere with the expression of Snail.E-cadherin,Nephrin,Desmin,and α-SMA were detected by Western blotting.Results After 24 hours of high glucose stimulation,PCR and Western blotting results showed that the expressions of NOD2 and Snail were significantly increased;the expressions of epithelial phenotype proteins E-cadherin and Nephrin were down-regulated;and the expressions of interstitial phenotype proteins Desmin and α-SMA were increased (all P ＜ 0.05);while there was no significant change in the hypertonic control group.After interference with NOD2,the abnormal expression of Snail and EMT related proteins were all recovered.After interference with Snail expression,Compared with the MDP group,the protein expressions of E-cadherin and Nephrin were significantly increased (all P ＜ 0.05);the expressions of Desmin and α-SMA were significantly decreased.Conclusions High glucose can induce NOD2 expression in podocytes,and promote podocyte epithelial-mesenchymal transition by upregulating Snail expression.Gene intervention targeting the NOD2/Snail/EMT pathway can reduce high-glucose-induced podocyte injury and may provide new ideas for the treatment of diabetic nephropathy.
