Division of Nephrology, West China Hospital of Sichuan University, Chengdu, Sichuan, China.
Nephrology (Carlton). 2012 Aug;17(6):552-60. doi: 10.1111/j.1440-1797.2012.01601.x.
To investigate the role of parathyroid hormone-related protein (PTHrP) in vascular calcification of patients with chronic hemodialysis.
The inferior epigastric arteries were obtained from 23 patients on chronic haemodialysis and 16 patients with renal carcinoma as control. Haematoxylin-eosin staining, elastic fibre staining, Alizarin Red calcium staining and immunohistochemical staining of PTHrP, bone morphogenetic protein-2 (BMP-2), Cbfa1/Runx2 were performed. Real-time polymerase chain reaction (PCR) was used to examine mRNA expressions of PTHrP, BMP-2 and Cbfa1/Runx2. Western blot and real-time PCR were used to detect the effects of PTHrP-siRNA and rh-PTHrP-1-34 on the expressions of PTHrP, BMP-2 and Cbfa1/Runx2 in human aortic smooth muscle cells (HASMC). Alkaline phosphatase (ALP) activities and intracellular calcium content in HASMCs were assessed after treatment with 10 mmol/L β-glycerol phosphoric acid for 48 h.
Vascular calcification was confirmed in 78.2% of patients on chronic haemodialysis, and the expressions of PTHrP, BMP-2 and Cbfa1 in the arteries were significantly upregulated. PTHrP-siRNA could downregulate the expression of PTHrP by 60%, BMP-2 by 25% and Cbfa1 by 25% at 24 h (P < 0.05). Exogenous rh-PTHrP-1-34 could upregulate the expressions of BMP-2 and Cbfa1 by 1.37-fold and 1.46-fold, respectively, at 24 h in a time-independent manner (P < 0.05), which were attenuated by PTHrP-siRNA. Moreover, it could promote intracellular calcium deposition and increase ALP activities, which were partially blocked by PTHrP-siRNA (P < 0.05).
Vascular calcification was common in patients with chronic haemodialysis, to which PTHrP might contribute by activating BMP-2/ Cbfa1 signalling pathway.
探讨甲状旁腺激素相关蛋白（PTHrP）在慢性血液透析患者血管钙化中的作用。
取 23 例慢性血液透析患者和 16 例肾细胞癌患者的下腹动脉。进行苏木精-伊红染色、弹性纤维染色、茜素红钙染色和 PTHrP、骨形态发生蛋白-2（BMP-2）、Cbfa1/Runx2 的免疫组织化学染色。采用实时聚合酶链反应（PCR）检测 PTHrP、BMP-2 和 Cbfa1/Runx2 的 mRNA 表达。采用 Western blot 和实时 PCR 检测 PTHrP-siRNA 和 rh-PTHrP-1-34 对人主动脉平滑肌细胞（HASMC）中 PTHrP、BMP-2 和 Cbfa1/Runx2 表达的影响。用 10mmol/Lβ-甘油磷酸处理 48h 后，检测 HASMC 的碱性磷酸酶（ALP）活性和细胞内钙含量。
78.2%的慢性血液透析患者存在血管钙化，动脉中 PTHrP、BMP-2 和 Cbfa1 的表达明显上调。PTHrP-siRNA 可使 HASMC 中 PTHrP 在 24h 时的表达下调 60%，BMP-2 下调 25%，Cbfa1 下调 25%（P<0.05）。外源性 rh-PTHrP-1-34 可在无时间依赖性的情况下，使 BMP-2 和 Cbfa1 在 24h 时的表达分别上调 1.37 倍和 1.46 倍（P<0.05），该作用可被 PTHrP-siRNA 阻断。此外，rh-PTHrP-1-34 还可促进细胞内钙沉积，增加 ALP 活性，而这些作用可被 PTHrP-siRNA 部分阻断（P<0.05）。
慢性血液透析患者中血管钙化较为常见，PTHrP 可能通过激活 BMP-2/Cbfa1 信号通路而导致该疾病的发生。
