High uric acid induces phenotypic transition of renal tubular cells via PI3K/Akt signaling pathway
10.3760/cma.j.issn.1001-7097.2018.02.008
- VernacularTitle:高尿酸通过PI3K/Akt信号通路促进肾小管上皮细胞转分化
- Author:
Xiaoyan XIONG
1
;
Shoujun BAI
;
Yakun WANG
;
Tingting JI
;
Hongxiu DU
;
Xiaoying LI
;
Congpu GAO
;
Juan LIU
;
Yingchun ZHU
;
Fangfang ZHA
Author Information
1. 复旦大学附属中山医院青浦分院肾内科
- Keywords:
Uric acid;
Kidney tubules;
Epithelial cells;
Epithelial-mesenchymal transition;
PI3K/Akt
- From:
Chinese Journal of Nephrology
2018;34(2):130-135
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effect and the mechanism of epithelial-mesenchymal transition (EMT) in renal tubular cells induced by uric acid.Methods Normal rat kidney tubular cell line (NRK-52E) were exposed to different concentrations of uric acid (100,200,400,600,800 μmol/L UA) for 48 hours to induce EMT.Morphological changes of the NRK-52E cells were examined under an inverted phase contrast microscope.The protein expression of E-cadherin,α-SMA,p-Akt and Akt were detected by Western blotting.The distribution of E-cadherin and α-SMA were detected by immunofluorescence.NRK-52E cells were pretreated by different concentrations of LY294002(0,2.5,5,10,15 μmol/L),the inhibitor of PI3K/p-Akt signaling pathway,and then processed by uric acid (400 μmol/L) for 48 hours.Western blotting was used to detect the protein expression of p-Akt and Akt.NRK-52E cells were then divided into four groups:normal group (N),uric acid group (UA),LY294002 group (LY),uric acid with LY294002 group (UA + LY).The protein expression of E-cadherin and α-SMA were detected by Western blotting,the distribution of E-cadherin,α-SMA and p-Akt were detected by immunofluorescence.Results There was abundant cellular expression of E-cadherin in unstimulated renal tubular cells whereas its expression was significantly decreased in uric acidstimulated cells (P ＜ 0.05).In addition,uric acid induced de novo expression of α-SMA in contrast to almost negative staining in untreated cells (P ＜ 0.05).p-Akt were obviously increased in high uric acid group (P ＜ 0.05) and Akt changed not significantly (P ＞ 0.05).NRK-52E cells transformed into elongated fibroblast-like cells from cuboidal clustered epithelial cells.These indicated that uric acid has induced EMT and activated PI3K/p-Akt signaling pathway in NRK-52E cells.However,the above effects of uric acid were abolished when p-Akt was blocked by the PI3K inhibitor (10,15 μmol/L LY294002),indicated that LY294002 has reversed the trend of EMT.Conclusions High uric acid induces phenotypic transition of renal tubular cells probably via activating PI3K/Akt signaling pathway.
