Rashid Gloria, Plotkin Eleanora, Klein Osnat, Green Janice, Bernheim Jacques, Benchetrit Sydney
Dept. of Nephrology and Hypertension, Meir Medical Center, Kfar-Saba, Tchernichovsky 59, Kfar-Saba 44281, Israel.
Am J Physiol Renal Physiol. 2009 Jan;296(1):F60-6. doi: 10.1152/ajprenal.00622.2007. Epub 2008 Oct 22.
Parathyroid hormone (PTH), which is elevated in patients with chronic renal failure, has been shown to participate in the development of vascular calcification. Previous studies have demonstrated that PTH may promote endothelial expressions of proinflammatory parameters. On the basis of these data, we evaluated whether PTH may have an impact on endothelial osteoprotegerin (OPG), a vascular-protective factor which may control vascular calcification. Endothelial cells were stimulated with 10(-12) to 10(-10) mol/l PTH. PKC and PKA are the main cellular pathways of PTH. Inhibitors and activators of PKC or PKA were used to determine whether these signaling pathways are involved in the control of endothelial OPG. PTH induced a decrease in OPG secretion and mRNA expression. Treatment of PTH-stimulated cells by calphostin C (PKC inhibitor) induced a further decrease in OPG secretion, while Rp-cAMP (PKA inhibitor) had no additional effect. In nonstimulated cells, a PKC activator significantly stimulated OPG secretion, while a PKA activator was associated with a decline. These effects were blunted in the presence of calphostin C and Rp-cAMP, respectively. An increase in OPG secretion induced by a PKC activator indicates that the basal OPG secretion is mediated through PKC. The decrease induced by a PKA activator, which is similar to the decrease observed with PTH, suggests that the action of PTH on OPG secretion and mRNA expression may be due to the PKA pathway.
甲状旁腺激素（PTH）在慢性肾衰竭患者中水平升高，已被证明参与血管钙化的发展。先前的研究表明，PTH可能促进促炎参数的内皮表达。基于这些数据，我们评估了PTH是否可能对内皮骨保护素（OPG）产生影响，OPG是一种可能控制血管钙化的血管保护因子。用10（-12）至10（-10）mol/L的PTH刺激内皮细胞。PKC和PKA是PTH的主要细胞途径。使用PKC或PKA的抑制剂和激活剂来确定这些信号通路是否参与内皮OPG的调控。PTH导致OPG分泌和mRNA表达减少。用钙泊三醇C（PKC抑制剂）处理PTH刺激的细胞导致OPG分泌进一步减少，而Rp-cAMP（PKA抑制剂）没有额外作用。在未刺激的细胞中，PKC激活剂显著刺激OPG分泌，而PKA激活剂则导致分泌下降。这些作用分别在钙泊三醇C和Rp-cAMP存在时减弱。PKC激活剂诱导的OPG分泌增加表明基础OPG分泌是通过PKC介导的。PKA激活剂诱导的下降，类似于PTH观察到的下降，表明PTH对OPG分泌和mRNA表达的作用可能归因于PKA途径。
