[Renal bioactivation of vitamin D and its key modulators].
Renal tubular cells bio-activates vitamin D, where 25-hydroxyvitamin D(3) (25D) is supplied to 1alpha hydroxylase, mitochondrial enzyme through apical endocytosis of 25D-binding protein complex. This intracellular trafficking depends on multiple endocytic receptor megalin. Megalin-null mouse harbors similar bone phenotype to vitamin D deficiency. 1alpha hydroxylase plays a key role for final activation of vitamin D, which is canonically regulated by parathyroid hormone (PTH) . Precise transcriptional regulation of this mitochondrial enzyme renders key downstream modulators : CCAAT enhancer binding protein (C/EBP) beta in mouse, vitamin D interacting repressor and vitamin D receptor in human. Fibroblast growth factor (FGF) 23, circulating phosphaturic hormone, has a counter-regulatory property against vitamin D bio-activation. FGF23 strongly inhibits 1alpha hydroxylase expression and its transcriptional activity. Recent study has demonstrated that FGF23 binds FGF receptor 1/klotho complex in tubular cells. Further studies will allow us to better understand the whole mechanism that regulates 1alpha hydroxylation in renal tubular cells by focusing on key molecules: C/EBPbeta, VDR, FGF23, klotho.
Sato
Tetsuhiko
T
Nagoya Daini Red Cross Hospital, Department of Transplant and Endocrine Surgery, Japan.
D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000378:metabolism; D000818:Animals; D002112:Calcifediol / Q000378:metabolism; D002117:Calcitriol / Q000096:biosynthesis; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000378:metabolism; D007668:Kidney / Q000378:metabolism*; D014807:Vitamin D / Q000378:metabolism*
C000717427:FGF23 protein, human; C000717428:Fgf23 protein, mouse; D014807:Vitamin D; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase; D002117:Calcitriol; D002112:Calcifediol