Decreased bone density and increased phosphaturia in gene-targeted mice lacking functional serum- and glucocorticoid-inducible kinase 3
| Autor: | Leticia Quintanilla-Martinez, Paola Capuano, Martin S. Judenhofer, Bernd J. Pichler, Mentor Sopjani, Dan Yang Huang, Carsten A. Wagner, Gerti Stange, Michael Föller, Madhuri Bhandaru, Balasaheb Siraskar, Jürg Biber, Ioana Alesutan, Anand Rotte, Leonid Tyan, David A. Pearce, Florian Lang, Ganesh Pathare, Daniela S. Kempe |
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| Přispěvatelé: | University of Zurich, Lang, F |
| Rok vydání: | 2011 |
| Předmět: |
Fibroblast growth factor 23
Bone density Xenopus Parathyroid hormone 030204 cardiovascular system & hematology 10052 Institute of Physiology Mice 0302 clinical medicine Bone Density mineralization Hypophosphatemia Familial Mice Knockout 0303 health sciences 2727 Nephrology Kinase Recombinant Proteins Kidney Tubules Nephrology 10076 Center for Integrative Human Physiology Knockout mouse Female PTH medicine.drug Signal Transduction insulin medicine.medical_specialty Calcitriol chemistry.chemical_element Biological Transport Active 610 Medicine & health Biology Calcium In Vitro Techniques Protein Serine-Threonine Kinases Sodium-Phosphate Cotransporter Proteins Type IIa Article Phosphates 03 medical and health sciences Internal medicine medicine Animals Humans Gene knockout phosphate 030304 developmental biology Endocrinology chemistry Oocytes 570 Life sciences biology 1 25(OH)2D3 |
| Zdroj: | Kidney international |
| ISSN: | 0085-2538 |
| DOI: | 10.1038/ki.2011.67 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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