Effects of urokinase -type plasminogen activator on high glucose-induced rat mesangial cells proliferation and phenotype transformation
10.3760/cma.j.issn.1001-7097.2011.07.013
- VernacularTitle:尿激酶型纤溶酶原激活物对高糖诱导大鼠系膜细胞增殖及表型转化的影响及其机制
- Author:
Hui CHENG
;
Guohua DING
;
Cheng CHEN
;
Ming SHI
;
Hongxia YANG
- Publication Type:Journal Article
- Keywords:
Urokinase-type plasminogen activator;
Mesangial cell;
Proliferation;
Signaling transduction
- From:
Chinese Journal of Nephrology
2011;27(7):515-519
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the effects and mechanisms of urokinase-type plasminogen activator (uPA) on high glucose-induced rat mesangial cells proliferation and phenotype transformation. Methods Rat mesangial cells were cultured and incubated in media containing either 5 mmol/L D-glucose or 30 mmol/L D-glucose with or without addition of wortmannin, or uPA (105 U/L) for different time periods. At the end of the incubation period, mesangial cells proliferation was assessed by MTT assay and flow cytometric analysis. Cyclin-dependent kinase 2 (CDK2) and p27kip1 expression and activation of Akt were evaluated by Western blotting and Akt kinase assay respectively. Furthermore, the expression and distribution of α-SMA were detected with laser confocal microscopy. Results MTT assay and flow cytometric analysis demonstrated that high glucose induced mesangial cells proliferation (P＜0.05) and an incresed proportion of cells in G2/M+S stage after 24 h incubation (P＜0.01), which were attenuated by uPA or wortmannin (P＜0.01). High glucose induced the enhance of Akt activity after 3 h (P＜0.05), and the effect was inhibited by wortmannin or uPA (P＜0.01). High glucose did not alter CDK2 expression (P＞0.05),but significantly inhibited p27kip1 expression (P＜0.05), which was attenuated by wortmannin or uPA (P＜0.01). High glucose induced the up-regulation of α-SMA expression and perinucleus location in mesangial cells after 24 h (P＜0.01), which were alleviated by wortmannin or uPA (P＜0.01). Conclusion uPA up-regulates p27kip1 expression and counteracts high glucose-induced mesangial cells proliferation and phenotype transformation via blocking PI3K-Akt signaling pathway.
