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NFκB-sensitive Orai1 expression in the regulation of FGF23 release
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نویسنده
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Zhang Bingbing ,Yan Jing ,Umbach Anja T. ,Fakhri Hajar ,Fajol Abul ,Schmidt Sebastian ,Salker Madhuri S. ,Chen Hong ,Alexander Dorothea ,Spichtig Daniela ,Daryadel Arezoo ,Wagner Carsten A. ,Föller Michael ,Lang Florian
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منبع
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journal of molecular medicine - 2016 - دوره : 94 - شماره : 5 - صفحه:557 -566
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چکیده
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Fibroblast growth factor (fgf23) plasma levels are elevated in cardiac and renal failure and correlate with poor clinical prognosis of those disorders. both disorders are associated with inflammation and activation of the inflammatory transcription factor nfκb. an excessive fgf23 level is further observed in klotho-deficient mice. the present study explored a putative sensitivity of fgf23 expression to transcription factor nfκb, which is known to upregulate orai1, the ca2+ channel accomplishing store-operated ca2+ entry (soce). in osteoblastic cells (umr106) and immortalized primary periosteal (ipo) cells, protein abundance was determined by western blotting, and in umr106 cells, transcript levels were quantified by rt-pcr, cytosolic ca2+ activity utilizing fura-2-fluorescence, and soce from ca2+ entry following store depletion by thapsigargin. as a result, umr106 and ipo cells expressed ca2+ channel orai1. soce was lowered by nfκb inhibitor wogonin as well as by orai1 inhibitors 2-apb and ym58483. umr106 cell fgf23 transcripts were increased by stimulation of soce and ca2+ ionophore ionomycin and decreased by orai inhibitors 2-apb, ym58483 and sk&f96365, by orai1 silencing, as well as by nfκb inhibitors wogonin, withaferin a, and cas 545380-34-5. in conclusion, fgf23 expression is upregulated by stimulation of nfκb-sensitive, store-operated ca2+ entry.
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کلیدواژه
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25(OH)2D3 ,SOCE ,Calcium ,Orai1 ,NFκB
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آدرس
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University of Tübingen, Department of Physiology, Germany, University of Tübingen, Department of Physiology, Germany, University of Tübingen, Department of Physiology, Germany, University of Tübingen, Department of Physiology, Germany, University of Tübingen, Department of Physiology, Germany, University of Tübingen, Department of Physiology, Germany, University of Tübingen, Department of Physiology, Germany, University of Tübingen, Department of Physiology, Germany, University Hospital of Tübingen, Department of Oral and Maxillofacial Surgery, Germany, University of Zürich, Switzerland, University of Zürich, Switzerland, University of Zürich, Switzerland, Martin Luther University Halle-Wittenberg, Germany, University of Tübingen, Department of Physiology, Germany
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Authors
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