Effect of aldosterone on epithelial-to-mesenchymal transition of human peritoneal mesothelial cells
Kidney Research and Clinical Practice
;
: 83-92, 2015.
Article
Dans Anglais
| WPRIM
| ID: wpr-50611
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.
Texte intégral:
Disponible
Indice:
WPRIM (Pacifique occidental)
Sujet Principal:
Péritoine
/
Phosphotransferases
/
Protein kinases
/
Système rénine-angiotensine
/
Spironolactone
/
Cadhérines
/
Technique de Western
/
Actines
/
Dialyse péritonéale
/
Espèces réactives de l'oxygène
Limites du sujet:
Humains
langue:
Anglais
Texte intégral:
Kidney Research and Clinical Practice
Année:
2015
Type:
Article
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