Institute of Agricultural and Nutritional Sciences, Martin-Luther University Halle-Wittenberg, D-06120, Halle (Saale), Germany.
Department of Physiology, Eberhard-Karls University of Tübingen, D-72076 Tübingen, Germany.
Sci Rep. 2017 Jul 10;7(1):4982. doi: 10.1038/s41598-017-05226-y.
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)D 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.
转化生长因子-β（TGF-β）是一种由多种细胞类型产生的细胞因子，涉及细胞生长、分化、凋亡和炎症。它通过钙释放激活钙（CRAC）通道 Orai1/Stim1 刺激储存操作钙内流（SOCE）在子宫内膜 Ishikawa 细胞中。成骨细胞产生成纤维细胞生长因子（FGF）23，它与共同受体 Klotho 一起抑制肾脏磷酸盐重吸收和 1,25(OH)D 的形成。此外，Klotho 和 FGF23 可抵抗衰老和与年龄相关的临床状况。FGF23 的产生依赖于 Orai1 介导的 SOCE 和炎症。在这里，我们探讨了 TGF-β2 在 FGF23 合成中的潜在作用。为此，培养 UMR106 成骨样细胞，通过 qRT-PCR 确定 Fgf23 转录物水平，通过 ELISA 测量 FGF23 蛋白，通过荧光光学分析 SOCE。UMR106 细胞表达 TGF-β 受体 1 和 2。TGF-β2 增强了 SOCE，并强烈刺激了 FGF23 的产生，这一效应被 TGF-β 类型 I 受体激活素受体样激酶 ALK5、ALK4 和 ALK7 的抑制剂 SB431542 显著减弱。此外，SOCE 抑制剂 2-APB 减弱了 TGF-β2 对 FGF23 产生的作用。我们得出结论，TGF-β2 诱导 FGF23 的产生，这一效应涉及 SOCE 的上调。
