TY - JOUR
T1 - Possible underlying mechanisms responsible for aldosterone and mineralocorticoid receptor-dependent renal injury
AU - Kiyomoto, Hideyasu
AU - Rafiq, Kazi
AU - Mostofa, Mahbub
AU - Nishiyama, Akira
N1 - Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2008
Y1 - 2008
N2 - There is increasing evidence indicating the roles of aldosterone and mineralocorticoid receptor (MR) in the pathogenesis of renal injury. In rats, chronic treatment with aldosterone and salt results in severe proteinuria and renal tissue injury, characterized by glomerulosclerosis and tubulointerstitial fibrosis. Aldosterone-induced renal tissue injury is associated with increases in reactive oxygen species (ROS) levels and activation of mitogen-activated protein kinases (MAPKs) or Rho-kinase. Treatment with a selective MR antagonist, eplerenone, prevents aldosterone-induced increases in ROS levels and MAPK activity and ameliorates renal injury. In vitro studies have revealed that MR is highly expressed in glomerular mesangial cells (RMCs), podocytes, and renal interstitial fibroblasts. In these renal cells, aldosterone induces cellular injury through NADPH oxidase-dependent ROS production and activation of MAPKs or Rho-kinase. Such aldosterone-induced renal cellular injury is markedly attenuated by treatment with eplerenone. These data suggest that aldosterone induces renal injury via activation of MR through mechanisms that cannot be simply explained by changes in blood pressure. In this review, we summarized recent findings on the roles of aldosterone and MR in the pathogenesis of renal injury with particular emphasis on potential underlying mechanisms.
AB - There is increasing evidence indicating the roles of aldosterone and mineralocorticoid receptor (MR) in the pathogenesis of renal injury. In rats, chronic treatment with aldosterone and salt results in severe proteinuria and renal tissue injury, characterized by glomerulosclerosis and tubulointerstitial fibrosis. Aldosterone-induced renal tissue injury is associated with increases in reactive oxygen species (ROS) levels and activation of mitogen-activated protein kinases (MAPKs) or Rho-kinase. Treatment with a selective MR antagonist, eplerenone, prevents aldosterone-induced increases in ROS levels and MAPK activity and ameliorates renal injury. In vitro studies have revealed that MR is highly expressed in glomerular mesangial cells (RMCs), podocytes, and renal interstitial fibroblasts. In these renal cells, aldosterone induces cellular injury through NADPH oxidase-dependent ROS production and activation of MAPKs or Rho-kinase. Such aldosterone-induced renal cellular injury is markedly attenuated by treatment with eplerenone. These data suggest that aldosterone induces renal injury via activation of MR through mechanisms that cannot be simply explained by changes in blood pressure. In this review, we summarized recent findings on the roles of aldosterone and MR in the pathogenesis of renal injury with particular emphasis on potential underlying mechanisms.
KW - Aldosterone
KW - Eplerenone
KW - Extracellular signal-regulated kinases (ERK) 1/2
KW - Kidney
KW - Mineralocorticoid receptor
KW - Reactive oxygen species (ROS)
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U2 - 10.1254/jphs.08R02CR
DO - 10.1254/jphs.08R02CR
M3 - Review article
C2 - 19057124
AN - SCOPUS:58149154840
VL - 108
SP - 399
EP - 405
JO - Journal of Pharmacological Sciences
JF - Journal of Pharmacological Sciences
SN - 1347-8648
IS - 4
ER -