The roles of vitamin D and growth factors in the pathogenesis of renal osteodystrophy

维生素D和生长因子在肾性骨营养不良发病机制中的作用

• 批准号: 06454353
• 负责人: SEINO Yoshiki
• 金额: $ 4.86万
• 依托单位: Okayama University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06454353/
• 关键词: vitamin D receptor; gene polymorphism; secondary hyperparathyroidism; 骨密度; ビタミンD受容体(VDR); IGF結合蛋白(IGFBP); 2次性副甲状腺機能亢進症(2ﾟHPT); 腎性骨異栄養症(ROD)

To clarify the pathophysiologic roles of vitamin D in the renal osteodystrophy, the expression of vitamin D receptor (VDR) gene in parathyroid gland was examined. Decreased expression of VDR was confirmed by immunostaining and in situ hybridization methods. From these results in hands, we next turned to examine the VDR gene polymorphism in renal failure, because Eisman et al.suggested that VDR gene polymorphism might determine VDR mRNA stability. Namely, the genotype which contains Bsml and Apal cutting sites in intron 8 (referred to as B and A respectively), and does not contain Taql cutting site (t) in exon 9 might be unstable. In chronic renal failure patients, the patients who had B,A,t genotype showed more sever from of secondary hyperparathyroidism. Therefore, the severities of secondary hyperparathyroidism may be forecasted by the analysis of VDR gene polymorphism.

为了阐明维生素D在肾骨营养不良中的病理生理作用，检查了维生素D受体（VDR）基因在甲状旁腺中的表达。通过免疫染色和原位杂交方法证实了VDR表达的降低。从这些结果中，我们接下来转向检查肾衰竭中的VDR基因多态性，因为Eisman等人认为VDR基因多态性可能决定VDR mRNA稳定性。也就是说，内含子8（分别称为B和A）中包含BSML和APAL切割位点的基因型，并且在9中不包含外显子9中不包含TAQL切割位点（T）可能不稳定。在慢性肾衰竭患者中，患有B，A，T基因型的患者与继发性甲状旁腺功能亢进症显示出更多的因素。因此，可以通过对VDR基因多态性的分析来预测继发性甲状旁腺功能亢进的严重性。

项目成果

S. Fujimoto: "Urinary Pyridinoline and Deoxypyridinoline in Healthy Children and in Children with Growth Hormone Deficiency." Journal of Clinical Endocrinology and Metabolism. 80. 1922-1928 (1995)

S. Fujimoto：“健康儿童和生长激素缺乏儿童的尿吡啶啉和脱氧吡啶啉。”

S.Wei: "A Multiple Assay for Vitamin D Metabolites without High-Performance Liquid Chromatography." Analytical Biochemistry. 222. 359-365 (1994)

S.Wei：“无需高效液相色谱法即可对维生素 D 代谢物进行多重测定。”

S.Wei: "A Multiple Assay for Vitamin D Metabolite without High-Performance Liquid Chromatography." Analytical Biochemistry. 222. 359-365 (1994)

S.Wei：“无需高效液相色谱法即可对维生素 D 代谢物进行多重测定。”

S.Kanzaki: "Evidence that human bone cells in culture produce insulin-like growth factor-binding protein-4 and -5 protease." Endocrinology. 134. 383-392 (1994)

S.Kanzaki：“有证据表明，培养的人骨细胞会产生胰岛素样生长因子结合蛋白-4 和-5 蛋白酶。”

T.Yamate: "Bone-Forming Ability of 24R,25-Dihydroxy-Vitamin D3 in the Hypophosphatemic Mouse. Patterns of Osteocalcin and its Propeptide." Journal of Bone and Mineral Research. 9. 1967-1974 (1994)

T.Yamate：“低磷血症小鼠中 24R,25-二羟基维生素 D3 的骨形成能力。骨钙素及其前肽的模式。”