PI3K/Akt signaling regulates epithelial-mesenchymal transition of peritoneal mesothelial cells in peritoneal dialysis
10.3760/cma.j.issn.1001-7097.2014.05.008
- VernacularTitle:PI3K/Akt信号调节腹膜间皮细胞上皮-间充质转分化
- Author:
Xiang PENG
;
Fuyou LIU
;
Lin SUN
;
Li XIAO
;
Ming WANG
;
Jun LI
- Publication Type:Journal Article
- Keywords:
Phosphatidylinositol 3-kimase;
Akt;
Peritoneal dialysis;
Peritoneal mesothelial cells;
Epithelial-mesenchymal transition
- From:
Chinese Journal of Nephrology
2014;30(5):363-369
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the role of PI3K/Akt signaling in the regulation of epithelial-mesenchymal transition (EMT) of peritoneal mesothelial cells (PMCs) in peritoneal dialysis in vitro and in vivo.Methods The level of Phosphorylated serine/threonine kinase Akt and the expression of EMT associated gene and protein,including ZO-1,Vimentin and FN,were measured in mice EMT model.In vitro study,phosphorylation level and nuclear translocation of Akt,ZO-1 and Vimentin expression induced by TGF-β1 in human peritoneal mesothelial cells (HPMCs) were also observed.Moreover,HPMCs were pre-treated by one of PI3K/Akt inhibitor,LY294002,or transfected with dominant-negative Akt plasmid to inhibit PI3K/Akt signaling,then analyzed its effect on Zo-1 and Vimentin expression induced by TGF-β1.Results Compared with the control,thickened parietal peritoneum and remarkable decrease in mRNA and protein of the epithelial marker ZO-1,and notable increased in the expression of mesenchymal markers Vimentin and FN were observed in PD mice (all P ＜ 0.01).Moreover,the phosphorylation of Akt also significantly increased under above condition (P ＜ 0.01).In vitro study,with the stimulation of TGF-β1,the expression of Zo-l was down-regulated,while the expression of Vimentin increased (all P ＜ 0.01).In addition,TGF-β1 remarkably increased pAkt in HPMCs (all P ＜ 0.01) in dose-dependent.However,LY294002 and DN-Akt dramatically inhibited the vimentin expression in HPMCs induced by TGF-β1 after inhibition of pAkt.On the other hand,the expression of ZO-1 also was restored (P ＜ 0.01).Conclusion PI3K/Akt signaling is involved in EMT of peritoneal mesothelial cells in peritoneal dialysis,and may be a new target for the prevention and treatment of peritoneal fibrosis during PD.
