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2015 ; 34
(2
): 83-92
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Effect of aldosterone on epithelial-to-mesenchymal transition of human peritoneal
mesothelial cells
#MMPMID26484027
Yu M
; Shin HS
; Lee HK
; Ryu DR
; Kim SJ
; Choi KB
; Kang DH
Kidney Res Clin Pract
2015[Jun]; 34
(2
): 83-92
PMID26484027
show ga
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, ?-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.