Effect of aldosterone on epithelial-to-mesenchymal transition of human peritoneal mesothelial cells.
10.1016/j.krcp.2015.03.005
- Author:
Mina YU
1
;
Hyun Soo SHIN
;
Hyeon Kook LEE
;
Dong Ryeol RYU
;
Seung Jung KIM
;
Kyu Bok CHOI
;
Duk Hee KANG
Author Information
1. Department of Internal Medicine, Seonam Hospital, Seoul, Korea.
- Publication Type:Original Article
- Keywords:
Aldosterone;
Epithelial-to-mesenchymal transition;
Mesothelial cell;
Peritoneal dialysis;
Peritoneal fibrosis
- MeSH:
Actins;
Aldosterone*;
Antioxidants;
Blotting, Western;
Cadherins;
Cysteine;
Epithelial Cells;
Humans;
p38 Mitogen-Activated Protein Kinases;
Peritoneal Dialysis;
Peritoneal Fibrosis;
Peritoneum;
Phosphotransferases;
Protein Kinases;
Reactive Oxygen Species;
Receptors, Mineralocorticoid;
Renin-Angiotensin System;
Spironolactone
- From:Kidney Research and Clinical Practice
2015;34(2):83-92
- CountryRepublic of Korea
- Language:English
-
Abstract:
BACKGROUND: Peritoneal fibrosis is one of the major causes of technical failure in patients on peritoneal dialysis. Epithelial-to-mesenchymal transition (EMT) of the peritoneum is an early and reversible mechanism of peritoneal fibrosis. Human peritoneal mesothelial cells (HPMCs) have their own renin-angiotensin-aldosterone system (RAAS), however, it has not been investigated whether aldosterone, an end-product of the RAAS, induces EMT in HPMCs, and which mechanisms are responsible for aldosterone-induced EMT. METHODS: EMT of HPMCs was evaluated by comparing the expression of epithelial cell marker, E-cadherin, and mesenchymal cell marker, alpha-smooth muscle actin after stimulation with aldosterone (1-100nM) or spironolactone. Activation of extracellular signal-regulated kinase (ERK)1/2 and p38 mitogen-activated protein kinase (MAPK) and generation of reactive oxygen species (ROS) were assessed by western blotting and 2',7'-dichlorofluororescein diacetate staining, respectively. The effects of MAPK inhibitors or antioxidants (N-acetyl cysteine, apocynin, and rotenone) on aldosterone-induced EMT were evaluated. RESULTS: Aldosterone induced EMT in cultured HPMCs, and spironolactone blocked aldosterone-induced EMT. Aldosterone induced activation of both ERK1/2 and p38 MAPK from 1 hour. Either PD98059, an inhibitor of ERK1/2, or SB20358, an inhibitor of p38 MAPK, attenuated aldosterone-induced EMT. Aldosterone induced ROS in HPMCs from 5 minutes, and antioxidant treatment ameliorated aldosterone-induced EMT. N-acetyl cysteine and apocynin alleviated activation of ERK and p38 MAPK. CONCLUSION: Aldosterone induced EMT in HPMCs by acting through the mineralocorticoid receptor. Aldosterone-induced generation of ROS followed by activation of ERK, and p38 MAPK served as one of the mechanisms of aldosterone-induced EMT of HPMCs.
