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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.
Sujets)

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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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