Effects of a novel PPARγ agonist on Wnt-β-catenin pathway in ADPKD cystic-lining epithelial cells
10.3760/cma.j.issn.1001-7097.2012.06.010
- VernacularTitle:新型过氧化物酶体增殖物激活受体激动剂对人多囊肾囊肿衬里上皮细胞Wnt-β连环素信号通路的影响
- Author:
Lili FU
;
Moyan LIU
;
Chunyan LIU
;
Huimin HU
;
Changlin MEI
- Publication Type:Journal Article
- Keywords:
PPAR gamma;
Polycystic kidney,autosomal dominant;
Proliferation;
Polycystic kidney cyst-lining epithelial cells;
Wnt-β-catenin
- From:
Chinese Journal of Nephrology
2012;28(6):464-468
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effects of a novel PPARγ agonist DH9 on Wntβ-catenin pathway in human polycystic kidney cystic-lining epithelial cells (WT9-12).Methods WT9-12 cells were treated with different concentrations of DH9 for 72 hours and the proliferation was assessed by MTT.WT9-12 cells were pretreated with SB216763 or GW9662 for two hours and then treated with DH9 for 72 hours.Western blotting was applied to detect the protein expression of β-catenin,phospho-β-catenin,GSK3β,phospho-GSK3β.Results DH9 could effectively inhibit the proliferation of the cells.60 μmol/L DH9 could facilitate β-catenin down-regulation (P＜0.01) and phospho-β-catenin up-regulation (P＜0.01).Inhibition of GSK3β by SB216763 could protect WT9-12 cells against DH9-facilitated β-catenin repression in a dose-dependent manner despite phosphorylating deactivation,but PPARγ inhibitor GW9662 couldn't.Conclusions DH9can effectively block the proliferation of WT9-12 cells.The effect may be mediated by facilitating the down-regulation of β-catenin via GSK3β-dependent mechanism.
