The role of vitamin D in the FGF23, klotho, and phosphate bone-kidney endocrine axis

摘要: 1,25-dihydroxyvitamin D (1,25D), through association with the nuclear vitamin receptor (VDR), exerts control over a novel endocrine axis consisting of bone-derived hormone FGF23, and kidney-expressed klotho, CYP27B1, CYP24A1 genes, which together prevent hyperphosphatemia/ectopic calcification govern levels 1,25D to maintain bone mineral integrity while promoting optimal function other vital tissues. When occupied by 1,25D, VDR interacts RXR form heterodimer that binds VDREs in region genes directly controlled (e.g., Npt2c, CYP27B1 CYP24A1). By recruiting complexes comodulators, activated initiates series events induces or represses transcription encoding proteins such as: osteocyte-derived hormone, FGF23; renal anti-senescence factor protein co-receptor for klotho; mediators phosphate transport including Npt2a/c; metabolic enzymes, CYP24A1. The mechanism whereby osteocytes are triggered release FGF23 is yet be fully defined, but phosphate, leptin appear play major roles. kidney responds elicit CYP24A1-catalyzed detoxification also repressing both Npt2a/c mediate elimination limit de novo synthesis. Comprehension these skeletal actions should facilitate development mimetics ectopic calcification, chronic vascular disease, promote healthful aging.