FGF-23 Regulates CYP27B1 Transcription in the Kidney and in Extra-Renal Tissues

• DOI: 10.1371/journal.pone.0072816
• Publication Date: 2013-09-03T21:13:25Z
• Authors: Ankanee Chanakul; Martin Y. H. Zhang; Andrew Louw; Harvey J. Armbrecht; Walter L. Miller; Anthony A. Portale; Farzana Perwad
• Keywords: Enzymologic; Transcription, Genetic; MAP Kinase Signaling System; Science; 610; Kidney; Real-Time Polymerase Chain Reaction; Gene Expression Regulation, Enzymologic; Promoter Regions; Mice; 03 medical and health sciences; Genetic; Animals; Humans; Promoter Regions, Genetic; 25-Hydroxyvitamin D3 1-alpha-Hydroxylase; 0303 health sciences; Q; R; Fibroblast Growth Factors; Fibroblast Growth Factor-23; HEK293 Cells; Gene Expression Regulation; Medicine; Transcription; Research Article

The mitochondrial enzyme 25-hydroxyvitamin D 1α-hydroxylase, which is encoded by the CYP27B1 gene, converts 25OHD to biological active form of vitamin D, 1,25-dihydroxyvitamin (1,25(OH)2D). Renal 1α-hydroxylase activity principal determinant circulating 1,25(OH)2D concentration and tightly regulated several factors. Fibroblast growth factor-23 (FGF-23) decreases serum concentrations suppressing mRNA abundance in mice. In extra-renal tissues, responsible for local synthesis, has important paracrine actions, but whether FGF-23 regulates gene expression tissues unknown. We sought determine transcription kidney are target sites FGF-23-induced suppression CYP27B1. HEK293 cells transfected with human promoter, suppressed promoter 70%, suppressive effect was blocked CI-1040, a specific inhibitor extracellular signal kinase 1/2. To examine transcriptional vivo, we crossed fgf-23 null mice bearing promoter-driven luciferase transgene (1α-Luc). null/1α-Luc mice, increased 3-fold compared that wild-type/1α-Luc Intraperitoneal injection renal protein 26% 60% respectively, PD0325901, an ERK1/2 inhibitor. These findings provide evidence suppresses kidney. Furthermore, demonstrate sites. heart were 2- 5-fold higher, than control also observed 3- 10-fold increase lung, spleen, aorta testis Thus, have identified novel FGF-23-mediated regulation