title: Blunted DOCA/high salt induced albuminuria and renal tubulointerstitial damage in gene-targeted mice lacking SGK1.
abstract: 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.
authors.affiliation: Department of Physiology, University of Tübingen, Gmelinstr. 5, 72076, Tübingen, Germany.
authors.forename: Ferruh
authors.initials: F
authors.lastname: Artunc
authors.forename: Kerstin
authors.initials: K
authors.lastname: Amann
authors.forename: Omaima
authors.initials: O
authors.lastname: Nasir
authors.forename: Björn
authors.initials: B
authors.lastname: Friedrich
authors.forename: Diana
authors.initials: D
authors.lastname: Sandulache
authors.forename: Nermina
authors.initials: N
authors.lastname: Jahovic
authors.forename: Teut
authors.initials: T
authors.lastname: Risler
authors.forename: Volker
authors.initials: V
authors.lastname: Vallon
authors.forename: Peer
authors.initials: P
authors.lastname: Wulff
authors.forename: Dietmar
authors.initials: D
authors.lastname: Kuhl
authors.forename: Florian
authors.initials: F
authors.lastname: Lang
mesh_terms: D000419:Albuminuria / Q000139:chemically induced* / Q000201:enzymology* / Q000503:physiopathology; D000818:Animals; D001794:Blood Pressure; D001835:Body Weight; D002118:Calcium / Q000652:urine; D003404:Creatinine / Q000652:urine; D003900:Desoxycorticosterone; D005247:Feeding Behavior; D018390:Gene Targeting; D006400:Hematocrit; D017874:Immediate-Early Proteins / Q000172:deficiency*; D007678:Kidney Glomerulus / Q000098:blood supply / Q000166:cytology / Q000473:pathology / Q000503:physiopathology; D007684:Kidney Tubules / Q000166:cytology / Q000201:enzymology / Q000473:pathology* / Q000503:physiopathology; D051379:Mice; D009395:Nephritis, Interstitial / Q000139:chemically induced* / Q000201:enzymology* / Q000503:physiopathology; D009929:Organ Size; D011188:Potassium / Q000652:urine; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency*; D012964:Sodium / Q000652:urine; D017673:Sodium Chloride, Dietary; D000099184:Serum-Glucocorticoid Regulated Kinases
chemical_list: D002118:Calcium; D003404:Creatinine; D003900:Desoxycorticosterone; D017874:Immediate-Early Proteins; D011188:Potassium; D017346:Protein Serine-Threonine Kinases; D012964:Sodium; D017673:Sodium Chloride, Dietary; D000099184:Serum-Glucocorticoid Regulated Kinases