Up-regulation of stanniocalcin 1 expression by 1,25-dihydroxy vitamin D3 and parathyroid hormone in renal proximal tubular cells

Abstract

Stanniocalcin 1 and stanniocalcin 2 are two glycoprotein hormones, which act as calcium phosphate-regulating factor on intestine and kidney. We have previously reported that stanniocalcin 2 expression is positively and negatively controlled by 1,25(OH)2D3 and parathyroid hormone in renal proximal tubular cells. However, it has been unclear whether they regulate the stanniocalcin 1 gene expression. In this study, we identified the opossum stanniocalcin 1 cDNA sequence. The opossum stanniocalcin 1 amino acid sequence had 83% homology with human stanniocalcin 1, and has a conserved putative N-linked glycosylation site. Real-time PCR analysis using opossum kidney proximal tubular (OK-P) cells revealed that the mRNA levels of stanniocalcin 1 gene is up-regulated by both 1,25(OH)2D3 and parathyroid hormone in dose-dependent and time-dependent manners. We also demonstrated that the stanniocalcin 1 expression was increased in parathyroid hormone injected rat kidney. Furthermore, the mRNA expression of stanniocalcin 1 and stanniocalcin 2 were oppositely regulated by phorbol 12,13-myristic acetate, a specific PKC activator. Interestingly, the up-regulation of stanniocalcin 1 gene by 1,25(OH)2D3 and phorbol 12,13-myristic acetate were not prevented in the presence of actinomycin D, an RNA synthesis inhibitor. These results suggest that the stanniocalcin 1 gene expression is up-regulated by 1,25(OH)2D3 and parathyroid hormone through mRNA stabilization in renal proximal tubular cells.

Reduced phosphorus intake throughout gestation and lactation of sows is mitigated by transcriptional adaptations in kidney and intestine

“…Interestingly, the STC1 (Stanniocalcin 1) gene, a glycoprotein hormone, was down-regulated in group H compared to M (FC: 1.83). It has been demonstrated that the expression of STC1 is induced by circulating Ca [31], calcitriol and PTH [32] in the kidney, and that STC1 stimulates P absorption in the small intestine and reabsorption in the proximal tubules of the kidney [33]. This suggests that a high intake of dietary P induces molecular mechanisms that counteract an oversupply with Ca and P of the organism.…”

Genetic variants of major genes contributing to phosphate and calcium homeostasis and their association with serum parameters in pigs

“…Due to increasing serum P levels and decreasing serum Ca levels, the G allele might be favorable with regard to hydroxyapatite deposition in bone (Madsen et al 1998 ). The analyzed SNP is located in the 3′UTR, which seems to be well conserved between mammalian species (Varghese et al 1998 ) and which was suggested to be important to understand the molecular mechanisms of gene regulation (Hung et al 2012 ). Furthermore, the involvement of STC1 in bone formation is supported by its location in a QTL for osteochondrosis-related traits in different pig populations (Lee et al 2003 ; Laenoi et al 2011 ) .…”

“…Also of interest is STC1 , as the encoded glycoprotein hormone stanniocalcin regulates P as well as Ca homeostasis in intestine and kidney (Ishibashi and Imai 2002 ). STC1 expression is upregulated by PTH and calcitriol in the kidney (Hung et al 2012 ). Previous experiments by Madsen et al ( 1998 ) showed a decreased Ca absorption, while P absorption was increased in swine intestine, which may enhance the deposition of hydroxyapatite into bone.…”

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

“…Additionally, given that it has been well established that Na + /Ca 2+ exchange is not the major mechanism underlying Ca 2+ efflux in enterocytes [ 23 ], the low impact of STC1 on NCX1 expression in Caco2 cells is not surprising. Furthermore, a previous report has shown that STC1 can be up-regulated by 1,25(OH) 2 D 3 in opossum kidneys [ 24 ]. However, we found that STC1 over-expression resulted in a significant inhibition of VDR mRNA levels as detected by real-time RT-PCR, while further marked effects on the protein expression were not investigated by the methods we employed.…”