Aldosterone induces mesangial cell apoptosis both in vivo and in vitro

Mathew, Jayant T.; Patni, Hitesh; Chaudhary, Ahmad N.; Liang, Wei; Gupta, Aakriti; Chander, Praveen N.; Ding, Guohua; Singhal, Pravin C.

doi:10.1152/ajprenal.00435.2007

Cited by 46 publications

(36 citation statements)

References 52 publications

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“…These findings are consistent with the hypothesis that aldosterone stimulates ROS generation through NADPH oxidase-dependent mechanisms (21). Recent studies show that aldosterone induces mesangial cell apoptosis and that administration of antioxidants, free radical scavengers, or MR blockers partially attenuates the proapoptotic effects of aldosterone (22).…”

Section: Renal Cell Injury Induced By Aldosterone and Its Possible Mesupporting

confidence: 90%

Possible Underlying Mechanisms Responsible for Aldosterone and Mineralocorticoid Receptor–Dependent Renal Injury

et al. 2008

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Abstract. 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 Rhokinase. 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.

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Section: Renal Cell Injury Induced By Aldosterone and Its Possible Mesupporting

confidence: 90%

Possible Underlying Mechanisms Responsible for Aldosterone and Mineralocorticoid Receptor–Dependent Renal Injury

et al. 2008

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“…Proapoptotic and mitogenic aldosterone-dependent effects that could be reduced by both MR antagonists and free radical scavengers were observed in cultured human mesangial cells (103). Furthermore, rats treated for a prolonged period of time with aldosterone showed enhanced mesangial cell proliferation and expansion of the mesangium (110).…”

Section: Potential Role Of Impaired Corticosteroid Regulation In Westmentioning

confidence: 99%

The Western-style diet: a major risk factor for impaired kidney function and chronic kidney disease

Odermatt

2011

American Journal of Physiology-Renal Physiology

210

128

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The Western-style diet is characterized by its highly processed and refined foods and high contents of sugars, salt, and fat and protein from red meat. It has been recognized as the major contributor to metabolic disturbances and the development of obesity-related diseases including type 2 diabetes, hypertension, and cardiovascular disease. Also, the Western-style diet has been associated with an increased incidence of chronic kidney disease (CKD). A combination of dietary factors contributes to the impairment of renal vascularization, steatosis and inflammation, hypertension, and impaired renal hormonal regulation. This review addresses recent progress in the understanding of the association of the Western-style diet with the induction of dyslipidemia, oxidative stress, inflammation, and disturbances of corticosteroid regulation in the development of CKD. Future research needs to distinguish between acute and chronic effects of diets with high contents of sugars, salt, and fat and protein from red meat, and to uncover the contribution of each component. Improved therapeutic interventions should consider potentially altered drug metabolism and pharmacokinetics and be combined with lifestyle changes. A clinical assessment of the long-term risks of whole-body disturbances is strongly recommended to reduce metabolic complications and cardiovascular risk in kidney donors and patients with CKD.

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“…Aldosterone promotes tissue inflammation and fibrosis and plays a role in cell proliferation and apoptosis. [1][2][3][4] Activation of the EGF receptor and mitogen-activated protein kinases (MAPK), induction of oxidative stress, and MR-dependent transcription of proinflammatory genes are some of the mechanisms proposed to account for the injurious effects induced by aldosterone. [5][6][7][8] As outlined by recent reports, mineralocorticoid also mediates inflammation and fibrosis through NF-B activation in liver, heart, and glomerular mesangial cells 9 -13 via a pathway involving the aldosterone early-induced gene, serum and glucocorticoid-induced kinase 1 (SGK1).…”

mentioning

confidence: 99%

Aldosterone Activates NF-κB in the Collecting Duct

Leroy

Seigneux²,

Agassiz³

et al. 2009

Journal of the American Society of Nephrology

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Besides its classical effects on salt homeostasis in renal epithelial cells, aldosterone promotes inflammation and fibrosis and modulates cell proliferation. The proinflammatory transcription factor NF-B has been implicated in cell proliferation, apoptosis, and regulation of transepithelial sodium transport. The effect of aldosterone on the NF-B pathway in principal cells of the cortical collecting duct, a major physiologic target of aldosterone, is unknown. Here, in both cultured cells and freshly isolated rat cortical collecting duct, aldosterone activated the canonical NF-B signaling pathway, leading to increased expression of several NF-B-targeted genes (IB␣, plasminogen activator inhibitor 1, monocyte chemoattractant protein 1, IL-1␤, and IL-6). Small interfering RNA-mediated knockdown of the serum and glucocorticoid-inducible kinase SGK1, a gene induced early in the response to aldosterone, but not pharmacologic inhibition of extracellular signal-regulated kinase and p38 kinase, attenuated aldosterone-induced NF-B activation. Pharmacologic antagonism or knockdown of the mineralocorticoid receptor prevented aldosterone-induced NF-B activity. In addition, activation of the glucocorticoid receptor inhibited the transactivation of NF-B by aldosterone. In agreement with these in vitro findings, spironolactone prevented NF-B-induced transcriptional activation observed in cortical collecting ducts of salt-restricted rats. In summary, aldosterone activates the canonical NF-B pathway in principal cells of the cortical collecting duct by activating the mineralocorticoid receptor and by inducing SGK1.

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Aldosterone induces mesangial cell apoptosis both in vivo and in vitro

Cited by 46 publications

References 52 publications

Possible Underlying Mechanisms Responsible for Aldosterone and Mineralocorticoid Receptor–Dependent Renal Injury

Possible Underlying Mechanisms Responsible for Aldosterone and Mineralocorticoid Receptor–Dependent Renal Injury

The Western-style diet: a major risk factor for impaired kidney function and chronic kidney disease

Aldosterone Activates NF-κB in the Collecting Duct

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