Vitamin D supplementation decreases TGF beta-1 bioavailability correlating with clinical improvement in Vitamin D deficient women with PCOS: a randomized placebo-controlled trial

Irani, Mohamad; Seifer, David B.; Grazi, Richard V.; Bhatt, Devika; Julka, Nitasha; Kalgi, Bharati; Irani, Sara; Tal, Oded; Tal, Reshef

doi:10.1016/j.fertnstert.2015.07.324

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“…1,25(OH) 2 D 3 inhibits downstream TGF-β signaling 25 . Vitamin D supplementation lowers the availability of TGF-β 26 . Downstream TGF-β and 1,25(OH) 2 D 3 signaling are characterized by intense crosstalk 27 .…”

Section: Discussionmentioning

confidence: 99%

The production of fibroblast growth factor 23 is controlled by TGF-β2

Feger

Hase

Zhang

et al. 2017

Sci Rep

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Transforming growth factor-β (TGF-β) is a cytokine produced by many cell types and implicated in cell growth, differentiation, apoptosis, and inflammation. It stimulates store-operated calcium entry (SOCE) through the calcium release-activated calcium (CRAC) channel Orai1/Stim1 in endometrial Ishikawa cells. Bone cells generate fibroblast growth factor (FGF) 23, which inhibits renal phosphate reabsorption and 1,25(OH)2D3 formation in concert with its co-receptor Klotho. Moreover, Klotho and FGF23 counteract aging and age-related clinical conditions. FGF23 production is dependent on Orai1-mediated SOCE and inflammation. Here, we explored a putative role of TGF-β2 in FGF23 synthesis. To this end, UMR106 osteoblast-like cells were cultured, Fgf23 transcript levels determined by qRT-PCR, FGF23 protein measured by ELISA, and SOCE analyzed by fluorescence optics. UMR106 cells expressed TGF-β receptors 1 and 2. TGF-β2 enhanced SOCE and potently stimulated the production of FGF23, an effect significantly attenuated by SB431542, an inhibitor of the transforming growth factor-β (TGF-β) type I receptor activin receptor-like kinases ALK5, ALK4, and ALK7. Furthermore, the TGF-β2 effect on FGF23 production was blunted by SOCE inhibitor 2-APB. We conclude that TGF-β2 induces FGF23 production, an effect involving up-regulation of SOCE.

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Section: Discussionmentioning

confidence: 99%