Renal Dnase1 expression is regulated by FGF23 but loss of Dnase1 does not alter renal phosphate handling

Abstract Fibroblast growth factor 23 (FGF23) is a bone-derived endocrine hormone that regulates phosphate and vitamin D metabolism. In models of FGF23 excess, renal deoxyribonuclease 1 (Dnase1) mRNA expression is downregulated. Dnase-1 is an endonuclease which binds monomeric actin. We investigated...

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Autores principales:	Daniela Egli-Spichtig, Martin Y. H. Zhang, Alfred Li, Eva Maria Pastor Arroyo, Nati Hernando, Carsten A. Wagner, Wenhan Chang, Farzana Perwad
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/89d7811941be4841a8aed0d4f045fe9c
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spelling	oai:doaj.org-article:89d7811941be4841a8aed0d4f045fe9c2021-12-02T13:18:09ZRenal Dnase1 expression is regulated by FGF23 but loss of Dnase1 does not alter renal phosphate handling10.1038/s41598-021-84735-32045-2322https://doaj.org/article/89d7811941be4841a8aed0d4f045fe9c2021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-84735-3https://doaj.org/toc/2045-2322Abstract Fibroblast growth factor 23 (FGF23) is a bone-derived endocrine hormone that regulates phosphate and vitamin D metabolism. In models of FGF23 excess, renal deoxyribonuclease 1 (Dnase1) mRNA expression is downregulated. Dnase-1 is an endonuclease which binds monomeric actin. We investigated whether FGF23 suppresses renal Dnase-1 expression to facilitate endocytic retrieval of renal sodium dependent phosphate co-transporters (NaPi-IIa/c) from the brush border membrane by promoting actin polymerization. We showed that wild type mice on low phosphate diet and Fgf23 −/− mice with hyperphosphatemia have increased renal Dnase1 mRNA expression while in Hyp mice with FGF23 excess and hypophosphatemia, Dnase1 mRNA expression is decreased. Administration of FGF23 in wild type and Fgf23 −/− mice lowered Dnase1 expression. Taken together, our data shows that Dnase1 is regulated by FGF23. In 6-week-old Dnase1 −/− mice, plasma phosphate and renal NaPi-IIa protein were significantly lower compared to wild-type mice. However, these changes were transient, normalized by 12 weeks of age and had no impact on bone morphology. Adaptation to low and high phosphate diet were similar in Dnase1 −/− and Dnase1 +/+ mice, and loss of Dnase1 gene expression did not rescue hyperphosphatemia in Fgf23 −/− mice. We conclude that Dnase-1 does not mediate FGF23-induced inhibition of renal tubular phosphate reabsorption.Daniela Egli-SpichtigMartin Y. H. ZhangAlfred LiEva Maria Pastor ArroyoNati HernandoCarsten A. WagnerWenhan ChangFarzana PerwadNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Daniela Egli-Spichtig Martin Y. H. Zhang Alfred Li Eva Maria Pastor Arroyo Nati Hernando Carsten A. Wagner Wenhan Chang Farzana Perwad Renal Dnase1 expression is regulated by FGF23 but loss of Dnase1 does not alter renal phosphate handling
description	Abstract Fibroblast growth factor 23 (FGF23) is a bone-derived endocrine hormone that regulates phosphate and vitamin D metabolism. In models of FGF23 excess, renal deoxyribonuclease 1 (Dnase1) mRNA expression is downregulated. Dnase-1 is an endonuclease which binds monomeric actin. We investigated whether FGF23 suppresses renal Dnase-1 expression to facilitate endocytic retrieval of renal sodium dependent phosphate co-transporters (NaPi-IIa/c) from the brush border membrane by promoting actin polymerization. We showed that wild type mice on low phosphate diet and Fgf23 −/− mice with hyperphosphatemia have increased renal Dnase1 mRNA expression while in Hyp mice with FGF23 excess and hypophosphatemia, Dnase1 mRNA expression is decreased. Administration of FGF23 in wild type and Fgf23 −/− mice lowered Dnase1 expression. Taken together, our data shows that Dnase1 is regulated by FGF23. In 6-week-old Dnase1 −/− mice, plasma phosphate and renal NaPi-IIa protein were significantly lower compared to wild-type mice. However, these changes were transient, normalized by 12 weeks of age and had no impact on bone morphology. Adaptation to low and high phosphate diet were similar in Dnase1 −/− and Dnase1 +/+ mice, and loss of Dnase1 gene expression did not rescue hyperphosphatemia in Fgf23 −/− mice. We conclude that Dnase-1 does not mediate FGF23-induced inhibition of renal tubular phosphate reabsorption.
format	article
author	Daniela Egli-Spichtig Martin Y. H. Zhang Alfred Li Eva Maria Pastor Arroyo Nati Hernando Carsten A. Wagner Wenhan Chang Farzana Perwad
author_facet	Daniela Egli-Spichtig Martin Y. H. Zhang Alfred Li Eva Maria Pastor Arroyo Nati Hernando Carsten A. Wagner Wenhan Chang Farzana Perwad
author_sort	Daniela Egli-Spichtig
title	Renal Dnase1 expression is regulated by FGF23 but loss of Dnase1 does not alter renal phosphate handling
title_short	Renal Dnase1 expression is regulated by FGF23 but loss of Dnase1 does not alter renal phosphate handling
title_full	Renal Dnase1 expression is regulated by FGF23 but loss of Dnase1 does not alter renal phosphate handling
title_fullStr	Renal Dnase1 expression is regulated by FGF23 but loss of Dnase1 does not alter renal phosphate handling
title_full_unstemmed	Renal Dnase1 expression is regulated by FGF23 but loss of Dnase1 does not alter renal phosphate handling
title_sort	renal dnase1 expression is regulated by fgf23 but loss of dnase1 does not alter renal phosphate handling
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/89d7811941be4841a8aed0d4f045fe9c
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Renal Dnase1 expression is regulated by FGF23 but loss of Dnase1 does not alter renal phosphate handling

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