Work

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

Year: 2021

Type: article

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 andFgf23−/−mice with hyperphosphatemia have increased renalDnase1mRNA expression while inHypmice with FGF23 excess and hypophosphatemia,Dnase1mRNA expression is decreased. Administration of FGF23 in wild type andFgf23−/−mice loweredDnase1expression. Taken together, our data shows thatDnase1is regulated by FGF23. In 6-week-oldDnase1−/−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 inDnase1−/−andDnase1+/+mice, and loss ofDnase1gene expression did not rescue hyperphosphatemia inFgf23−/−mice. We conclude that Dnase-1 does not mediate FGF23-induced inhibition of renal tubular phosphate reabsorption.

Source: Scientific Reports

DOI: 10.1038/s41598-021-84735-3