细胞凋亡
钙敏感受体
基因沉默
内质网
血管平滑肌
拟钙质
下调和上调
细胞生物学
标记法
分子生物学
生物
内分泌学
内科学
医学
钙
钙代谢
生物化学
基因
平滑肌
作者
Fen-fen Liu,Aihua Zhang,Hongdong Huang,Xu Liu,Zong-li Diao,Dai Deng,Wenhu Liu
出处
期刊:CardioRenal Medicine
[S. Karger AG]
日期:2022-01-01
卷期号:12 (5-6): 214-228
摘要
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 and subsequently protects HAoSMCs from high-phosphate-induced apoptosis.HAoSMCs were cultured, and STC2 expression was determined by qPCR. A calcimimetic (NPS R-568) or calcilytic (NPS-2143) was applied to HAoSMCs. STC2 mRNA and protein levels were measured by qPCR and Western blot, respectively, and confocal microscopy was employed to investigate subcellular localization. STC2 overexpression and silencing were induced to assess the effects of STC2 on high-phosphate-induced apoptosis, which was determined by caspase-3 levels and TUNEL staining. The anti-apoptotic effect of CaSR-induced STC2 was confirmed by interfering with STC2 expression in the presence of NPS R-568.The constitutive expression of STC2 was confirmed. STC2 mRNA and protein levels were increased by NPS R-568 with or without high phosphate. NPS-2143 resulted in decreased STC2 mRNA levels, but decreased STC2 protein levels were only found under the high-phosphate condition. Confocal microscopy demonstrated the colocalization of STC2 and plasma membrane or endoplasmic reticulum markers. STC2 overexpression reduced HAoSMCs apoptosis, which were reversed with STC2 silencing. NPS R-568 treatment reduced HAoSMCs apoptosis, but STC2 silencing abolished the protective effect.This is the first evidence that STC2 is regulated by CaSR in HAoSMCs. CaSR activation-induced STC2 has putative anti-apoptotic effects against high phosphate. Calcimimetics are promising agents to treat uremic vascular injury.
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