Study of signaling pathway of LDL and oxLDL inducing kidney tubular epithelial cells transdifferentiation
- VernacularTitle:低密度脂蛋白和氧化低密度脂蛋白诱导人肾小管上皮细胞转分化的通路研究
- Author:
Guoqin WANG
;
Hequn ZOU
;
Min LI
;
Ling CHEN
- Publication Type:Journal Article
- Keywords:
Low density lipoproteins;
Mitogen-activated protein kinases;
Transdifferentiation
- From:
Chinese Journal of Nephrology
1997;0(01):-
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore whether LDL and oxLDL may induce kidney tubular epithelial-mesenchymal transition (EMT) and its mechanism. Methods The second generation human kidney tubular epithelial cells (TECs) were cultured for 24 hours in different conditions as (1) serum free as control, (2) treated with LDL (50 ?g/ml) , (3) treated with oxLDL(50 ?g/ml), (4) treated with LDL(50 ?g/ml) plus PD98059(5 ?mlo/L) , (5) treated with oxLDL(50 ?g/ml) plus PD98059 (5 ?mol/L). The expression of cytokeratin, E-cadherin, ?-SMA and vimentin was assessed by immunofluorescence and Western-blot. Western-blot was also performed to test the expression of collagen I and phospho-ERKl/2MAPK and phospho-GSK-3?. Results oxLDL was more potently in inducing tubular EMT than LDL at 24 hours as demonstrated by de novo a-SMA expression, increased expression of vimentin, partial loss of cytokeratin and reduction of E-cadherin expression by TECs. The expression of collagen I and phospho-ERKl/2MAPK and phospho-GSK-3? was increased in TECs stimulated by LDL or oxLDL. MAPK inhibitor (PD98059) inhibited the phosphorylation of GSK-3P and almost completely blocked oxLDL-induced tubular EMT. However, PD98059 alone was able to inhibit LDL-induced tubular EMT partially. Conclusions oxLDL is more potently in inducing tubular EMT than LDL. The ERKl/2MAPK-GSK-3? signaling pathway mediates the LDL or oxLDL-induced tubular EMT.
