Regulation of Intestinal Epithelial Calcium Transport Proteins by Stanniocalcin-1 in Caco2 Cells.

Jinmei Xiang,Chunyun Wan,Shijin Yang,Rui Guo,Liming Wu,Dingzong Guo

doi:10.3390/ijms17071095

Abstract

Stanniocalcin-1 (STC1) is a calcium and phosphate regulatory hormone. However, the exact molecular mechanisms underlying how STC1 affects Ca2+ 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.

Highlights

Calcium (Ca2+) is an essential ion required for critical physiological processes in almost all organisms
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We have identified that over-expression of STC1 inhibits gene and protein expression of the epithelial Ca2+ channels TRPV5/6, TRPV6, a principal mechanism of Ca2+ transport across intestinal epithelia

Summary

Introduction

Calcium (Ca2+) is an essential ion required for critical physiological processes in almost all organisms. The transcellular route requires energy and occurs predominantly in the proximal small intestine, renal distal convoluted tubules and the connecting tubules in response to Ca2+ demands [2]. Ca2+ influx occurs at the apical membrane via epithelial Ca2+ channels (ECaC), which include the transient receptor potential vanilloid (TRPV) members 5 and 6 [1]. This step is considered to be the rate-limiting step for transcellular Ca2+ transport [1]; Second, intracellular diffusion is facilitated by vitamin D-dependent Ca2+-binding proteins calbindin-D9K and calbindin-D28K [3]; Last, extrusion at the bInats.

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