Aldosterone-stimulated SGK1 Activity Mediates Profibrotic Signaling in the Mesangium

Overview

Journal J Am Soc Nephrol

Specialty Nephrology

Date 2008 Jan 11

PMID 18184857

Citations 23

Authors

Yoshio Terada

Hitoshi Kuwana

Takahiko Kobayashi

Tomokazu Okado

Noriko Suzuki

Takanobu Yoshimoto

Yukio Hirata

Sei Sasaki

Affiliations

Soon will be listed here.

Abstract

Several recent reports support the hypothesis that aldosterone contributes to the progression of renal injury. Mineralocorticoids increase the expression of serum- and glucocorticoid-inducible protein kinase 1 (SGK1), which is upregulated in several fibrotic diseases. It was hypothesized that SGK1 may mediate the effects of aldosterone on glomerular fibrosis and inflammation. In primary cultures of rat mesangial cells, aldosterone stimulated the expression, phosphorylation, and kinase activity of SGK1, as well as SGK1-dependent NF-kappaB activity. Furthermore, aldosterone augmented the promoter activity and protein expression of intercellular adhesion molecule-1 (ICAM-1), which modulates the inflammatory response, and the profibrotic cytokine connective tissue growth factor (CTGF) in an SGK1- and NF-kappaB-dependent manner. Similar to the in vitro results, uninephrectomized rats that were treated with aldosterone demonstrated increased glomerular expression of SGK1, ICAM-1, and CTGF proteins than untreated rats; these changes were accompanied by hypertension, glomerulosclerosis, and inflammation. In conclusion, these findings suggest that aldosterone stimulates ICAM-1 and CTGF transcription via the activation of SGK1 and NF-kappaB, effects that may contribute to the progression of aldosterone-induced mesangial fibrosis and inflammation.

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