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OSR1-sensitive renal tubular phosphate reabsorption


Pathare, Ganesh; Föller, Michael; Daryadel, Arezoo; Mutig, Kerim; Bogatikov, Evgeny; Fajol, Abul; Almilaji, Ahmad; Michael, Diana; Stange, Gerti; Voelkl, Jakob; Wagner, Carsten A; Bachmann, Sebastian; Lang, Florian (2012). OSR1-sensitive renal tubular phosphate reabsorption. Kidney & Blood Pressure Research, 36(1):149-161.

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 (osr1(tg/+)) 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 osr1(tg/+) mice as compared to osr1(+/+) mice. Serum PTH and calcitriol levels were similar in osr1(tg/+) mice and in osr1(+/+) mice, serum FGF23 concentration was, however, significantly higher in osr1(tg/+) 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.

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 (osr1(tg/+)) 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 osr1(tg/+) mice as compared to osr1(+/+) mice. Serum PTH and calcitriol levels were similar in osr1(tg/+) mice and in osr1(+/+) mice, serum FGF23 concentration was, however, significantly higher in osr1(tg/+) 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.

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Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Physiology
07 Faculty of Science > Institute of Physiology

04 Faculty of Medicine > Center for Integrative Human Physiology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:26 October 2012
Deposited On:18 Dec 2012 16:16
Last Modified:07 Dec 2017 17:14
Publisher:Karger
ISSN:1420-4096
Additional Information:The final, published version of this article is available at http://www.karger.com/?doi=10.1159/000343405
Publisher DOI:https://doi.org/10.1159/000343405
PubMed ID:23095210

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