title: Decreased bone density and increased phosphaturia in gene-targeted mice lacking functional serum- and glucocorticoid-inducible kinase 3.
abstract: Insulin and growth factors activate the phosphatidylinositide-3-kinase pathway, leading to stimulation of several kinases including serum- and glucocorticoid-inducible kinase isoform SGK3, a transport regulating kinase. Here, we explored the contribution of SGK3 to the regulation of renal tubular phosphate transport. Coexpression of SGK3 and sodium-phosphate cotransporter IIa significantly enhanced the phosphate-induced current in Xenopus oocytes. In sgk3 knockout and wild-type mice on a standard diet, fluid intake, glomerular filtration and urine flow rates, and urinary calcium ion excretion were similar. However, fractional urinary phosphate excretion was slightly but significantly larger in the knockout than in wild-type mice. Plasma calcium ion, phosphate concentration, and plasma parathyroid hormone levels were not significantly different between the two genotypes, but plasma calcitriol and fibroblast growth factor 23 concentrations were significantly lower in the knockout than in wild-type mice. Moreover, bone density was significantly lower in the knockouts than in wild-type mice. Histological analysis of the femur did not show any differences in cortical bone but there was slightly less prominent trabecular bone in sgk3 knockout mice. Thus, SGK3 has a subtle but significant role in the regulation of renal tubular phosphate transport and bone density.
authors: Department of Physiology, University of Tübingen, Tübingen, Germany.
authors: Madhuri
authors: M
authors: Bhandaru
authors: Daniela S
authors: DS
authors: Kempe
authors: Anand
authors: A
authors: Rotte
authors: Paola
authors: P
authors: Capuano
authors: Ganesh
authors: G
authors: Pathare
authors: Mentor
authors: M
authors: Sopjani
authors: Ioana
authors: I
authors: Alesutan
authors: Leonid
authors: L
authors: Tyan
authors: Dan Yang
authors: DY
authors: Huang
authors: Balasaheb
authors: B
authors: Siraskar
authors: Martin S
authors: MS
authors: Judenhofer
authors: Gerti
authors: G
authors: Stange
authors: Bernd J
authors: BJ
authors: Pichler
authors: Jürg
authors: J
authors: Biber
authors: Leticia
authors: L
authors: Quintanilla-Martinez
authors: Carsten A
authors: CA
authors: Wagner
authors: David
authors: D
authors: Pearce
authors: Michael
authors: M
authors: Föller
authors: Florian
authors: F
authors: Lang
mesh_terms: D000818:Animals; D001693:Biological Transport, Active; D015519:Bone Density / Q000235:genetics / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D005260:Female; D006801:Humans; D007015:Hypophosphatemia, Familial / Q000201:enzymology / Q000209:etiology* / Q000235:genetics; D066298:In Vitro Techniques; D007684:Kidney Tubules / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009865:Oocytes / Q000378:metabolism; D010710:Phosphates / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D050613:Sodium-Phosphate Cotransporter Proteins, Type IIa / Q000235:genetics / Q000378:metabolism; D014981:Xenopus; D000099184:Serum-Glucocorticoid Regulated Kinases
chemical_list: D002118:Calcium; D010710:Phosphates; D017346:Protein Serine-Threonine Kinases; D011994:Recombinant Proteins; D050613:Sodium-Phosphate Cotransporter Proteins, Type IIa; C493554:SLC34A1 protein, human; C403243:SGK3 protein, human; D000099184:Serum-Glucocorticoid Regulated Kinases; C523602:Sgk3 protein, mouse