Xiang Jinmei, Guo Rui, Wan Chunyun, Wu Liming, Yang Shijin, Guo Dingzong
College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, Hubei, China.
Department of Animal Science, Hubei Vocational College Of Bio-Technology, Wuhan 430070, Hubei, China.
Int J Mol Sci. 2016 Jul 9;17(7):1095. doi: 10.3390/ijms17071095.
Stanniocalcin-1 (STC1) is a calcium and phosphate regulatory hormone. However, the exact molecular mechanisms underlying how STC1 affects Ca(2+) uptake remain unclear. Here, the expression levels of the calcium transport proteins involved in transcellular transport in Caco2 cells were examined following over-expression or inhibition of STC1. These proteins include the transient receptor potential vanilloid members (TRPV) 5 and 6, the plasma membrane calcium ATPase 1b (PMCA1b), the sodium/calcium exchanger (NCX1), and the vitamin D receptor (VDR). Both gene and protein expressions of TRPV5 and TRPV6 were attenuated in response to over-expression of STC1, and the opposite trend was observed in cells treated with siRNASTC1. To further investigate the ability of STC1 to influence TRPV6 expression, cells were treated with 100 ng/mL of recombinant human STC1 (rhSTC1) for 4 h following pre-transfection with siRNASTC1 for 48 h. Intriguingly, the increase in the expression of TRPV6 resulting from siRNASTC1 was reversed by rhSTC1. No significant effect of STC1 on the expression of PMCA1b, NCX1 or VDR was observed in this study. In conclusion, the effect of STC1 on calcium transport in intestinal epithelia is due to, at least in part, its negative regulation of the epithelial channels TRPV5/6 that mediate calcium influx.
骨钙素-1(STC1)是一种钙和磷调节激素。然而,STC1影响Ca(2+)摄取的具体分子机制仍不清楚。在此,在过表达或抑制STC1后,检测了Caco2细胞中参与跨细胞转运的钙转运蛋白的表达水平。这些蛋白包括瞬时受体电位香草酸受体成员(TRPV)5和6、质膜钙ATP酶1b(PMCA1b)、钠/钙交换器(NCX1)和维生素D受体(VDR)。TRPV5和TRPV6的基因和蛋白表达在STC1过表达时减弱,在用siRNASTC1处理的细胞中观察到相反的趋势。为了进一步研究STC1影响TRPV6表达的能力,在用siRNASTC1预转染48小时后,用100 ng/mL重组人STC1(rhSTC1)处理细胞4小时。有趣的是,rhSTC1逆转了siRNASTC1导致的TRPV6表达增加。在本研究中未观察到STC1对PMCA1b、NCX1或VDR表达的显著影响。总之,STC1对肠道上皮细胞钙转运的影响至少部分归因于其对介导钙内流的上皮通道TRPV5/6的负调节。