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Research Article
Liu F.-F. · Zhang A.-H. · Huang H.-D. · Liu X. · Diao Z.-L. · Deng D. · Liu W.
Introduction Apoptosis of vascular smooth muscle cells induced by hyperphosphatemia is a critical mechanism of chronic kidney disease-related vascular disorders. The present study investigated whether extracellular calcium-sensing receptor (CaSR) regulates stanniocalcin 2 (STC2) expression in HAoSMCs in vitro and whether induced STC2 protects HAoSMCs from high phosphate-induced apoptosis. Methods and Results The constitutive expression of STC2 was confirmed in cultured HAoSMCs. STC2 mRNA and protein levels were increased significantly by calcimimetic NPS R-568 at a concentration of 1 microM with or without high phosphate. Conversely, calcilytic NPS-2143 at a concentration of 1 microM resulted in significantly decreased STC2 mRNA levels regardless of whether high phosphate was present, but decreased STC2 protein levels were only found under the high phosphate condition. Confocal microscopy demonstrated colocalization of STC2 and plasma membrane or endoplasmic reticulum markers. STC2 overexpression significantly reduced caspase-3 levels in HAoSMCs with or without high phosphate, whereas STC2 silencing resulted in significantly increased caspase-3 levels. TUNEL staining revealed the same tendency. Similar to STC2 overexpression, NPS R-568 treatment significantly reduced caspase-3 levels in HAoSMCs, but STC2 silencing abolished the protective effect of NPS R-568, which was also supported by TUNEL staining. Conclusion This is the first evidence that STC2 is regulated by CaSR in HAoSMCs. CaSR activation and the subsequent STC2 increase have putative anti-apoptotic effects against high phosphate. Thus, calcimimetics are promising agents to treat vascular injury associated with uremia.
The Author(s). Published by S. Karger AG, Basel
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