Peroxisome proliferator–activated receptor α (PPARα)–dependent regulation of fibroblast growth factor 23 (FGF23)
| Autor: | Franz Ewendt, Frank Hirche, Michael Föller, Martina Feger |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Fibroblast growth factor 23 medicine.medical_specialty Physiology Clinical Biochemistry Down-Regulation Peroxisome proliferator-activated receptor Parathyroid hormone Phosphates 03 medical and health sciences Paracrine signalling 0302 clinical medicine Cell Line Tumor Physiology (medical) Internal medicine medicine Animals PPAR alpha Receptor chemistry.chemical_classification Osteoblasts Kinase NF-kappa B AMPK Lipid metabolism Rats Fibroblast Growth Factors Fibroblast Growth Factor-23 stomatognathic diseases 030104 developmental biology Endocrinology Gene Expression Regulation chemistry 030217 neurology & neurosurgery |
| Zdroj: | Pflügers Archiv - European Journal of Physiology. 472:503-511 |
| ISSN: | 1432-2013 0031-6768 |
| Popis: | 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 FGF23 in large part. Silencing of Orai-1 resulted in failure of PPARα to significantly influence Fgf23 expression. Taken together, PPARα is a potent regulator of FGF23. PPARα agonists down-regulate FGF23 formation at least in part through AMPK-mediated suppression of SOCE. |
| Databáze: | OpenAIRE |
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