Peroxisome proliferator-activated receptor α (PPARα)-dependent regulation of fibroblast growth factor 23 (FGF23).

Peroxisome proliferator-activated receptor α (PPARα)-dependent regulation of fibroblast growth factor 23 (FGF23). Pflugers Arch. 2020 Mar 18;: Authors: Ewendt F, Hirche F, Feger M, Föller M Abstract Bone cells secrete fibroblast growth factor 23 (FGF23), a hormone that inhibits the synthesis of active vitamin D (1,25(OH)2D3) and induces phosphate excretion in the kidney. In addition, it exerts paracrine effects on other cells including hepatocytes, cardiomyocytes, and immune cells. The production of FGF23 is controlled by different factors including parathyroid hormone, 1,25(OH)2D3, alimentary phosphate, insulin, inflammation, and AMP-dependent kinase (AMPK) regulation of store-operated Ca2+ entry (SOCE). Peroxisome proliferator-activated receptor α (PPARα) is a transcription factor with anti-inflammatory properties regulating lipid metabolism. Fibrates, PPARα agonists, are used in the treatment of dyslipidemia and activate AMPK. Here, we tested whether PPARα is a regulator of FGF23. Fgf23 gene expression was analyzed in UMR106 rat osteoblast-like cells by qRT-PCR, AMPK phosphorylation by Western blotting, and SOCE assessed by fluorescence optics. PPARα agonists fenofibrate and WY-14643 suppressed, whereas PPARα antagonist GW6471 and siRNA-mediated knockdown of PPARα induced Fgf23 gene expression. Fenofibrate induced AMPK activity in UMR106 cells and lowered SOCE. AMPK inhibitor compound C abrogated the PPARα effect on FGF...
Source: Pflugers Archiv : European Journal of Physiology - Category: Physiology Authors: Tags: Pflugers Arch Source Type: research