کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2779586 | 1153275 | 2012 | 8 صفحه PDF | دانلود رایگان |

Ectopic calcification of soft tissues can have severe clinical consequences especially when localized to vital organs such as heart, arteries and kidneys. Mammalian stanniocalcin (STC) 1 and 2 are glycoprotein hormones identified as calcium/phosphate-regulating hormones. The mRNA of STCs is upregulated in the kidney of α-klotho mutant (kl/kl) mice, which have hypercalcemia, hyperphosphatemia and hypervitaminosis D and exhibit a short life span, osteopenia and ectopic calcification. In the present study, we investigated the distribution and localization of STCs in kl/kl mice. Quantitative RT-PCR revealed that renal mRNA expression of STC2 was increased in both kl/kl mice and fibroblast growth factor 23 (Fgf23)-null mice compared with wild type mice. Interestingly, STC2 protein was focally localized with the calcified lesions of renal arterioles, renal tubular cells, heart and aorta in kl/kl mice. In vitro analysis of rat aortic vascular smooth muscle (A-10) cells showed that inorganic phosphate (Pi) stimulation significantly increased STC2 mRNA levels as well as that of osteocalcin, osteopontin and the type III sodium-dependent phosphate co-transporter (PiT-1), and induced STC2 secretion. Interestingly, the knockdown with a small interfering RNA or the over-expression of STC2 showed acceleration and inhibition of Pi-induced calcification in A-10 cells, respectively. These results suggest that the up-regulation of STC2 gene expression resulting from abnormal α-klotho-Fgf23 signaling may contribute to limitation of ectopic calcification and thus STC2 represents a novel target gene for cardio-renal syndrome.
► Renal STC2 expression was increased in both kl/kl mice and FGF23-null mice.
► STC2 protein co-localized with calcified lesions of kidney, heart and aorta in kl/kl mice.
► Inorganic phosphate (Pi) stimulated STC2 expression in rat aortic vascular smooth muscle (A-10) cells.
► STC2 inhibited Pi-induced calcification in A-10 cells.
Journal: Bone - Volume 50, Issue 4, April 2012, Pages 998–1005