title: OSR1-sensitive renal tubular phosphate reabsorption.
abstract: BACKGROUND
  The oxidative stress-responsive kinase 1 (OSR1) participates in the WNK-(with no K) kinase dependent regulation of renal salt excretion and blood pressure. Little is known, however, about the role of OSR1 in the regulation of further renal transport systems. The present study analyzed the effect of OSR1 on NaPiIIa, the major renal tubular phosphate transporter.
  
  
  METHODS
  Immunohistochemistry and confocal microscopy were employed to determine renal localization of OSR1 and NaPiIIa. To elucidate the effect of OSR on NaPiIIa activity, cRNA encoding NaPiIIa was injected into Xenopus oocytes with or without additional injection of cRNA encoding OSR1, and phosphate transport was estimated from phosphateinduced currents determined with dual electrode voltage clamp. To elucidate the in vivo significance of OSR1 serum phosphate and hormone concentrations as well as urinary phosphate output of mice carrying one allele of WNK-resistant OSR1 (osr1tg/(+)) were compared to the respective values of wild type mice (osr1(+/+)).
  
  
  RESULTS
  NaPiIIa and OSR1 were both expressed in proximal renal tubule cells. Coexpression of OSR1 significantly up-regulated phosphate-induced currents in NaPiIIa-expressing Xenopus oocytes. Despite decreased serum phosphate concentration urinary phosphate excretion was significantly increased and NaPiIIa protein abundance in the brush border membrane significantly reduced in osr1tg/(+) mice as compared to osr1(+/+) mice. Serum PTH and calcitriol levels were similar in osr1tg/(+) mice and in osr1(+/+) mice, serum FGF23 concentration was, however, significantly higher in osr1tg/(+) mice than in osr1(+/+) mice.
  
  
  CONCLUSIONS
  OSR1 is expressed in proximal renal tubules and participates in the regulation of FGF23 release and renal tubular phosphate transport.
authors.affiliation: Department of Physiology, University of Tübingen, Gmelinstr. 5, D-72076 Tübingen, Germany.
authors.forename: Ganesh
authors.initials: G
authors.lastname: Pathare
authors.forename: Michael
authors.initials: M
authors.lastname: Föller
authors.forename: Arezoo
authors.initials: A
authors.lastname: Daryadel
authors.forename: Kerim
authors.initials: K
authors.lastname: Mutig
authors.forename: Evgeny
authors.initials: E
authors.lastname: Bogatikov
authors.forename: Abul
authors.initials: A
authors.lastname: Fajol
authors.forename: Ahmad
authors.initials: A
authors.lastname: Almilaji
authors.forename: Diana
authors.initials: D
authors.lastname: Michael
authors.forename: Gerti
authors.initials: G
authors.lastname: Stange
authors.forename: Jakob
authors.initials: J
authors.lastname: Voelkl
authors.forename: Carsten A
authors.initials: CA
authors.lastname: Wagner
authors.forename: Sebastian
authors.initials: S
authors.lastname: Bachmann
authors.forename: Florian
authors.initials: F
authors.lastname: Lang
mesh_terms: D000042:Absorption / Q000502:physiology; D000818:Animals; D002117:Calcitriol / Q000097:blood; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood; D007684:Kidney Tubules / Q000378:metabolism*; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D009865:Oocytes / Q000166:cytology / Q000378:metabolism; D010281:Parathyroid Hormone / Q000097:blood; D018408:Patch-Clamp Techniques; D010710:Phosphates / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism*; D050613:Sodium-Phosphate Cotransporter Proteins, Type IIa / Q000378:metabolism*; D014982:Xenopus laevis
chemical_list: C000717428:Fgf23 protein, mouse; D010281:Parathyroid Hormone; D010710:Phosphates; C493555:Slc34a1 protein, mouse; D050613:Sodium-Phosphate Cotransporter Proteins, Type IIa; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; C534421:OXSR1 protein, mouse; D017346:Protein Serine-Threonine Kinases; D002117:Calcitriol