High glucose induces renal epithelial-mesenchymal transition through transforming growth factor β1-Smad signaling pathway
- VernacularTitle:高糖通过转化生长因子β1-Smad信号传递途径诱导肾小管上皮细胞转分化
- Author:
Feifei ZHANG
;
Ruoyun TAN
;
Mingxia XIONG
;
Xiaohua WANG
;
Li FANG
;
Wei FAN
;
Xiaoyun WANG
;
Junwei YANG
- Publication Type:Journal Article
- Keywords:
Transforming growth factor beta;
Diabetic nephropathy;
Kidney tubule;
Smad;
Epithelial-mesenchymM transition
- From:
Chinese Journal of Nephrology
2008;24(3):174-178
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effect of high glucose on renal tubular epithelial-mesenchymal transition,and to analyze the relationship between high glucose and transforming growth factor β1(TGF-β1)and the mechanism of renal interstitial fibrosis. Methods HKC and Smad7-overexpression HKC cells were grown in DMEM/F12 medium containing 5%～10%newborn calf serum.They were cultured for 16 h in free serum medium after 80%cells were adhered onto the surface of the flask.Afterwards,they were stimulated by high glucose(glucose concentration:25 mmol/L and 50 mmol/L).The expression of α-SMA,E-cadherin and fibronectin was detected by Western blot while the supernatant level of TGF-β1 was detected by ELISA.Cell motility and migration was evaluated using Boyden chamber motogenicity assay. Results In HKC induced by high glucose,the expression of α-SMA and fibronectin protein was highly upregulated while the expression of E-cadhefin protein was down-regulated.The expression of TGF-β1was up-regulated in a dose-dependent manner.These above-mentioned effects could be obviously inhibited by anti-TGF-β1 antibody.The protein expression of α-SMA,fibronectin and E-cadherin had no obvious change in Smad7-overexpression HKC induced by high glucose.HKC exhibited enhanced motility and invasive capacity in high glucose groups,compared to that in control group.Migrated cell counting was(12.4±3.7)and(18.6±4.4)cell/HP in 25 and 50 mmol/L glucose groups respectively. Conclusion High glucose may induce renal tubular epithelialmesenchymal transition through TGF-β1 pathway,which can be inhibited by blocking the Smad signal pathway.
