Department of Anatomy, Histology and Forensic Medicine, University of Firenze, Firenze, Italy.
J Nephrol. 2012 Jul-Aug;25(4):577-81. doi: 10.5301/jn.5000035.
In addition to its role in calcium homeostasis and bone mineralization, vitamin D is involved in immune defence, cardiovascular function, inflammation and angiogenesis, and these pleiotropic effects are of interested in the treatment of chronic kidney disease. Here we investigated the effects of paricalcitol, a nonhypercalcemic vitamin D analogue, on human peripheral blood mononuclear cell proliferation and signaling, and on angiogenesis. These effects were compared with those of a known inhibitor of angiogenesis pertaining to the vitamin D axis, the vitamin D-binding protein-derived Gc-macrophage activating factor (GcMAF).
Since the effects of vitamin D receptor agonists are associated with polymorphisms of the gene coding for the receptor, we measured the effects of both compounds on mononuclear cells harvested from subjects harboring different BsmI polymorphisms.
Paricalcitol inhibited mononuclear cell viability with the bb genotype showing the highest effect. GcMAF, on the contrary, stimulated cell proliferation, with the bb genotype showing the highest stimulatory effect. Both compounds stimulated 3'-5'-cyclic adenosine monophosphate formation in mononuclear cells with the highest effect on the bb genotype. Paricalcitol and GcMAF inhibited the angiogenesis induced by proinflammatory prostaglandin E1.
Polymorphisms of the vitamin D receptor gene, known to be associated with the highest responses to vitamin D receptor agonists, are also associated with the highest responses to GcMAF. These results highlight the role of the vitamin D axis in chronic kidney disease, an axis which includes vitamin D, its receptor and vitamin D-binding protein-derived GcMAF.
除了在钙稳态和骨矿化中的作用外，维生素 D 还参与免疫防御、心血管功能、炎症和血管生成，这些多效作用在慢性肾脏病的治疗中受到关注。在这里，我们研究了非高钙血症维生素 D 类似物帕立骨化醇对人外周血单核细胞增殖和信号转导以及血管生成的影响。将这些作用与维生素 D 轴的一种已知的血管生成抑制剂即维生素 D 结合蛋白衍生的 Gc-巨噬细胞激活因子（GcMAF）进行了比较。
由于维生素 D 受体激动剂的作用与编码受体的基因的多态性有关，我们测量了这两种化合物对携带不同 BsmI 多态性的受试者分离的单核细胞的作用。
帕立骨化醇抑制单核细胞活力，bb 基因型的作用最高。相反，GcMAF 刺激细胞增殖，bb 基因型的刺激作用最高。两种化合物均刺激单核细胞中 3'-5'-环磷酸腺苷的形成，bb 基因型的作用最高。帕立骨化醇和 GcMAF 抑制促炎前列腺素 E1 诱导的血管生成。
维生素 D 受体基因的多态性与对维生素 D 受体激动剂的最高反应有关，也与对 GcMAF 的最高反应有关。这些结果突出了维生素 D 轴在慢性肾脏病中的作用，该轴包括维生素 D、其受体和维生素 D 结合蛋白衍生的 GcMAF。
