Effects and Mechanism Study of Pioglitazone on High Glucose-induced Epithelial-mesenchymal Transition in Renal Tubular Epithelial Cells of Rat
- VernacularTitle:吡格列酮对高糖诱导的大鼠肾小管上皮细胞-间充质细胞转分化的影响及机制研究
- Author:
Lan SUN
1
;
Fan ZHANG
1
;
Mingjun SHI
1
;
Pingping TIAN
1
;
Bing GUO
2
Author Information
1. Dept. of Pathophysiology，College of Basic Medicine，Guizhou Medical University，Guiyang 550025，China;Guizhou Provincial Key Laboratory of Pathogenesis & Drug Research on Common Chronic Diseases，Guiyang 550025，China
2. Dept. of Pathophysiology，College of Basic Medicine，Guizhou Medical University，Guiyang 550025，China
- Publication Type:Journal Article
- Keywords:
Pioglitazone;
Renal tubular epithelial cell;
PPARγ;
PTEN;
PI3K/AKT signaling pathway;
Epithelial-mesenchymal
- From:
China Pharmacy
2020;31(16):1949-1954
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE：To investigate the effects o f pioglitazone （PIO）on high glucose-induced epithelial-mesenchymal transition（EMT）in renal tubular epithelial cells of rat and its possible mechanism ，and to provide theoretic reference and new target for the prevention and treatment of diabetic nephropathy. METHODS ：The rat renal tubular epithelial NRK- 52E cells were randomly divided into control group （5.5 mmol/L glucose ），high-glucose group （30 mmol/L glucose ），PIO intervention group （30 mmol/L glucose+ 5.0 μmol/L PIO），GW9662 intervention group （30 mmol/L glucose+ 5.0 μmol/L PIO+5.0 μmol/L specific anta- gonist GW 9662）. The cells of the first 3 groups were detected at 6，12，24，48 h of culture ，while those in GW 9662 intervention group were detected at 48 h of culture. mRNA expression of PTEN and PPARγ were detected by real-time PCR. The protein expression of PTEN ，PPARγ，α-SMA and E-cadherin as well as the changes of PI 3K/AKT signaling pathway were determined by Western blotting assay. RESULTS ：With the extension of culture time ，compared with control group ，the mRNA and protein expression of PPARγ（except for protein expression at 6 h）and PTEN in high-glucose group reduced significantly ，while the protein expression of α-SMA and p-AKT （Thr308）increased significantly ，and the protein expression of E-cadherin reduced significantly （P＜0.05），showing time-dependent trend. Compared with high-glucose group ，the mRNA and the protein expression （except for 6 h） of PPAR γ and PTEN were increased significantly in PIO intervention group ， while the protein expression of α-SMA and p-AKT （Thr308） were decreased significantly，and the protein expression of E-cadherin wasincreased significantly （P＜0.05）， showing time-dependent trend. There was no statistical significance in mRNA and protein expression of PPAR γ and PTEN，protein expression of E-cadherin ，α-SMA and p-AKT （Thr308） between GW 9662 intervention group and high-glucose group ；the effect of PIO was blocked by PPAR γ antagonist GW9662. CONCLUSIONS ：PIO may up-regulate the expression of PTEN by activating PPARγ，inhibit PI 3K/AKT signaling pathway so as to inhibit the occurrence of EMT of renal tubular epithelial cells .
