Fajol Abul, Honisch Sabina, Zhang Bingbing, Schmidt Sebastian, Alkahtani Saad, Alarifi Saud, Lang Florian, Stournaras Christos, Föller Michael
Department of Physiology, University of Tübingen, Germany.
Department of Zoology, Science College, King Saud University, Riyadh, Saudi Arabia.
FEBS Lett. 2016 Mar;590(6):705-15. doi: 10.1002/1873-3468.12096. Epub 2016 Feb 27.
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.
成纤维细胞生长因子23（FGF23）调节肾脏磷酸盐和维生素D代谢。FGF23缺失会导致大量钙化和快速衰老。1,25-二羟维生素D3（1,25(OH)2D3）和核因子κB（NFκB）信号传导可刺激FGF23的产生。在此，我们报告，用1,25(OH)2D3处理UMR106成骨样细胞，诱导Fgf23转录，导致肌动蛋白聚合，而这种聚合被NFκB抑制剂汉黄芩素阻断。有趣的是，肌动蛋白微丝破坏剂细胞松弛素B以及对肌动蛋白调节的Rac1/PAK1信号传导的抑制，消除了1,25(OH)2D3诱导的Fgf23基因转录。我们的结果提供了强有力的证据，表明由Rac1/PAK1途径调节的肌动蛋白重新分布参与了1,25(OH)2D3诱导的Fgf23基因转录。
