Blunted DOCA/high salt induced albuminuria and renal tubulointerstitial damage in gene-targeted mice lacking SGK1

• Published in: Journal of molecular medicine (Berlin, Germany) Vol. 84; no. 9; pp. 737 - 746
• Main Authors: ARTUNC, Ferruh, AMANN, Kerstin, LANG, Florian, NASIR, Omaima, FRIEDRICH, Björn, SANDULACHE, Diana, JAHOVIC, Nermina, RISLER, Teut, VALLON, Volker, WUIFF, Peer, KUHL, Dietmar
• Format: Journal Article
• Language: English
• Published: Berlin Springer 01.09.2006; Springer Nature B.V
• Subjects: Albuminuria - chemically induced; Albuminuria - enzymology; Albuminuria - physiopathology; Animals; Biological and medical sciences; Blood Pressure; Body Weight; Calcium - urine; Creatinine - urine; Desoxycorticosterone; Feeding Behavior; Gene Targeting; General aspects; Hematocrit; Immediate-Early Proteins - deficiency; Kidney Glomerulus - blood supply; Kidney Glomerulus - cytology; Kidney Glomerulus - pathology; Kidney Glomerulus - physiopathology; Kidney Tubules - cytology; Kidney Tubules - enzymology; Kidney Tubules - pathology; Kidney Tubules - physiopathology; Medical sciences; Mice; Nephritis, Interstitial - chemically induced; Nephritis, Interstitial - enzymology; Nephritis, Interstitial - physiopathology; Nephrology. Urinary tract diseases; Organ Size; Potassium - urine; Protein-Serine-Threonine Kinases - deficiency; Sodium - urine; Sodium Chloride, Dietary; Urinary system involvement in other diseases. Miscellaneous; Urinary tract. Prostate gland; High; Hormone; Urinary system disease; Targeting; Glycoprotein; Rodentia; Kidney; Medicine; Salt; Signal transduction; Vertebrata; Mammalia; Urinary system; Gene; Sodium; Mouse; Animal; Collagen; Hormones, Physiology; Genetics; Physiology; Lesion; Proteinuria
• ISSN: 0946-2716; 1432-1440
• DOI: 10.1007/s00109-006-0082-0

Mineralocorticoids stimulate renal tubular Na(+) reabsorption, enhance salt appetite, increase blood pressure, and favor the development of renal fibrosis. The effects of mineralocorticoids on renal tubular Na(+) reabsorption and salt appetite involve the serum- and glucocorticoid-inducible kinase 1 (SGK1). The kinase is highly expressed in fibrosing tissue. The present experiments thus explored the involvement of SGK1 in renal fibrosis. To this end, SGK1-knockout mice (sgk1 (-/-)) and their wild-type littermates (sgk1 (+/+)) were implanted with desoxycorticosterone acetate (DOCA)-release pellets and offered 1% saline as drinking water for 12 weeks. The treatment led to significant increases in fluid and Na(+) intake and urinary output of fluid and Na(+) in sgk1 (+/+) mice, effects blunted in sgk1 (-/-) mice. Blood pressure increased within the first 7 weeks to a similar extent in both genotypes, but within the next 5 weeks, it increased further only in sgk1 (+/+) mice. Creatinine clearance did not change significantly but albuminuria increased dramatically in sgk1 (+/+) mice, an effect significantly blunted in sgk1 (-/-) mice. Histology after 12 weeks treatment revealed marked glomerular sclerosis and tubulointerstitial damage with interstitial fibrosis and inflammation in kidneys from sgk1 (+/+) mice, but not from sgk1 (-/-) mice. In conclusion, a lack of SGK1 protects against DOCA/high-salt-induced albuminuria and renal fibrosis.