Stanniocalcin-1 Regulates Ca2+/Pi Uptake in Bovine Renal Tubule Epithelial Cells by Modulating Expression of Entry Channels In vitro

Stanniocalcin-1 (STC1), a glycoprotein, serves as an autocrine or paracrine factor in multiple processes in mammals, including the regulation of calcium/phosphorus (Ca 2+ /Pi) transport.However, its underlying mechanisms are not fully elucidated.Here, we examined the intracellular Ca 2+ ([Ca + ] i ) and Pi concentrations ([Pi]i) levels in primary bovine renal tubular epithelial cells (RTECs) using flow cytometry and phosphomolybdic spectrophotometry, respectively, following STC1 overexpression/ inhibition, and treatments with vitamin D3 receptor (VDR) agonist calcitriol or antagonist MeTC7.The expression of Ca 2+ /Pi transporters (TRPV5, TRPV6, CB-D28K, PMCA1b, NCX1, Npt2a, Npt2c) was measured by real-time qPCR and western blotting.The results revealed STC1 inhibition by STC1-shRNA promoted Ca 2+ intake and inhibited Pi influx, whereas STC1 overexpression by pcDNA3.1/STC1had the opposite effects.The calcitriol-induced increase in [Ca + ] i was reversed by STC1 overexpression and MeTC7 treatment.Overexpression of STC1 reduced the expression of TRPV5, TRPV6, and VDR, while suppressing calcitriol-induced TRPV5 upregulation and enhancing Npt2a/Npt2c expression.STC1 had no effect on CB-D28K, NCX1, or PMCA1b, which mediate Ca 2+ diffusion and extrusion.In conclusion, our findings suggest STC1 inhibits Ca 2+ transport and enhances Pi uptake in RTECs at least partly by regulating TRPV5/ TRPV6 and Npt2a/Npt2c expression, respectively.Interference of 1,25 (OH)2D3/VDR axis may also contribute.The present findings provide new insights into the underlying mechanisms of STC1 and offer strategies to prevent mineral disorders in cattle.