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Cited by 1Parathyroid Disorders and TreatmentsAlkaline Phosphatase Research StudiesIon Transport and Channel Regulation

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

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Egli-Spichtig, Daniela, Zhang, Martin Y. H., Li, Alfred, Pastor Arroyo, Eva Maria, Hernando, Nati, Wagner, Carsten A., Chang, Wenhan, Perwad, Farzana·2021·Scientific Reports
DOI 10.1038/s41598-021-84735-3PMC PMC7969776
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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.

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  • In rodent studies, renal Klotho expression is upregulated with low dietary Pi and downregulated with high dietary Pi.

    “Similarly, in rodent studies, renal Klotho expression—the main source of plasma soluble Klotho [38]—is upregulated and downregulated with low and high dietary Pi, respectively [18, 40].”

    From Controlled dietary phosphate loading in healthy young men elevates plasma phosphate and FGF23 levels (2025) · cites this paper as [18]

    The Results section on dietary phosphate reports higher renal Klotho mRNA in Dnase1−/− mice than in wild-type mice fed a low-phosphate diet. That is a genotype comparison, not evidence that lowering dietary phosphate upregulates Klotho; the section does not report Klotho downregulation with a high-phosphate diet. The Discussion’s low/high-diet upregulation and downregulation finding concerns Dnase1, not Klotho (page numbers unavailable). (LLM, conf=0.83)

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Authors
Egli-Spichtig, D., Zhang, M. Y. H., Li, A., Pastor Arroyo, E. M., Hernando, N., Wagner, C. A., Chang, W., & Perwad, F.
Affiliations
  • University of California, San Francisco (US)
  • San Francisco VA Medical Center (US)
  • University of Zurich (CH)
Corresponding author
Perwad, Farzana
ORCID
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2021-03-17
Volume
11
Issue
1
Pages
6175-6175
ISSN
2045-2322 (ISSN-L)
DOI
10.1038/s41598-021-84735-3
PMC
PMC7969776
OpenAlex
W3138775833
Cited by
1
References
0
Citations by year
2024: 1
FWCI
0.17
Type
journal article
Language
en
Open access
Licence
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, cc-by)
  • eScholarship (California Digital Library) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • eScholarship (California Digital Library) (submittedVersion)
  • Zurich Open Repository and Archive (University of Zurich) (submittedVersion, cc-by)
  • Zurich Open Repository and Archive (University of Zurich)
Funders
  • Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (P2ZHP3_161989)
  • Novartis Stiftung für Medizinisch-Biologische Forschung (#17B060)
  • CTSI-SOS
Topics
  • Health Sciences › Medicine › Nephrology › Parathyroid Disorders and Treatments
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Alkaline Phosphatase Research Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion Transport and Channel Regulation
Keywords
DNase1, fibroblast growth factor 23, renal phosphate reabsorption, NaPi-IIa, actin polymerization, hyperphosphatemia, hypophosphatemia, phosphate homeostasis, renal brush border membrane
MeSH terms
Fibroblast Growth Factor-23, Animals, Deoxyribonuclease I, Fibroblast Growth Factors, Kidney, Mice, Inbred C57BL, Phosphates, Hypophosphatemia, Mice, Knockout, Mice, Hyperphosphatemia

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