title: Fibroblast growth factor (Fgf) 23 gene transcription depends on actin cytoskeleton reorganization.
abstract: FGF23 regulates renal phosphate and vitamin D metabolism. Loss of FGF23 results in massive calcification and rapid aging. FGF23 production is stimulated by 1,25(OH)2D3 and NFκB signaling. Here, we report that treatment of UMR106 osteoblast-like cells with 1,25(OH)2D3, inducing Fgf23 transcription, resulted in actin polymerization which was blocked by NFκB inhibitor wogonin. Interestingly, 1,25(OH)2D3-induced Fgf23 gene transcription was abolished by the actin microfilament-disrupting agent cytochalasin B, as well as by the inhibition of actin-regulating Rac1/PAK1 signaling. Our results provide strong evidence that actin redistribution regulated by the Rac1/PAK1 pathway participates in 1,25(OH)2D3-induced Fgf23 gene transcription.
authors.affiliation: Department of Physiology, University of Tübingen, Germany.
authors.forename: Abul
authors.initials: A
authors.lastname: Fajol
authors.affiliation: Department of Physiology, University of Tübingen, Germany.
authors.forename: Sabina
authors.initials: S
authors.lastname: Honisch
authors.affiliation: Department of Physiology, University of Tübingen, Germany.
authors.forename: Bingbing
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Physiology, University of Tübingen, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Schmidt
authors.affiliation: Department of Zoology, Science College, King Saud University, Riyadh, Saudi Arabia.|Department of Biochemistry, University of Crete Medical School, Heraklion, Greece.
authors.forename: Saad
authors.initials: S
authors.lastname: Alkahtani
authors.affiliation: Department of Zoology, Science College, King Saud University, Riyadh, Saudi Arabia.|Department of Biochemistry, University of Crete Medical School, Heraklion, Greece.
authors.forename: Saud
authors.initials: S
authors.lastname: Alarifi
authors.affiliation: Department of Physiology, University of Tübingen, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Lang
authors.affiliation: Department of Physiology, University of Tübingen, Germany.|Department of Biochemistry, University of Crete Medical School, Heraklion, Greece.
authors.forename: Christos
authors.initials: C
authors.lastname: Stournaras
authors.affiliation: Institute of Agricultural and Nutritional Sciences, Martin-Luther University Halle-Wittenberg, Halle (Saale), Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Föller
mesh_terms: D008841:Actin Cytoskeleton / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D002117:Calcitriol / Q000378:metabolism / Q000494:pharmacology; D002460:Cell Line; D003571:Cytochalasin B / Q000494:pharmacology; D005346:Fibroblast Growth Factors / Q000096:biosynthesis / Q000235:genetics*; D044950:Flavanones / Q000494:pharmacology; D018613:Microscopy, Confocal; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D014158:Transcription, Genetic / Q000187:drug effects; D054462:p21-Activated Kinases / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000378:metabolism
chemical_list: C505605:Fgf23 protein, rat; D044950:Flavanones; D016328:NF-kappa B; D003571:Cytochalasin B; D005346:Fibroblast Growth Factors; C515906:Pak1 protein, rat; D054462:p21-Activated Kinases; C499134:Rac1 protein, rat; D020830:rac1 GTP-Binding Protein; D002117:Calcitriol; C085514:wogonin
keywords: PAK1; Rac1; Vitamin D; actin polymerization; cytochalasin B; fibroblast growth factor 23