成纤维细胞生长因子-23和α-Klotho蛋白在慢性肾脏病中的作用  

Role of fibroblast growth factor-23 and α-Klotho protein in chronic kidney disease

作　　者：张宝玉[1] 赵冬[1] 夏维波[2] 

机构地区：[1]首都医科大学附属北京潞河医院内分泌科,北京市糖尿病重点防治实验室,北京101149 [2]中国医学科学院北京协和医学院北京协和医院内分泌科国家卫生和计划生育委员会(原卫生部)内分泌重点实验室,北京100730

出　　处：《中华骨质疏松和骨矿盐疾病杂志》2015年第4期367-373,共7页Chinese Journal Of Osteoporosis And Bone Mineral Research

基　　金：国家自然科学基金(81471088)

摘　　要：成纤维细胞生长因子23(fibroblast growth factor 23,FGF-23)是一种重要的调磷因子,可以减少钠-磷共转运体NPT2a和NPT2c表达,增加尿磷的排泄;抑制1-α羟化酶(Cyp27b1)活性,刺激24-羟化酶(Cyp24α1)活性,减少血液中1,25(OH)2D3;减少甲状旁腺素(parathyroid hornone,PTH)分泌。α-Klotho蛋白是一种与抗衰老相关的单跨膜蛋白,膜型α-Klotho蛋白作为辅助因子与FGF受体(FGFR)组成聚合体,增强FGF-23与FGFR亲和力。分泌型α-Klotho蛋白不依赖于FGF-23而发挥作用,在近端小管细胞顶端膜区域通过聚糖酶修饰作用,促进Ca2+回吸收,灭活NPT2a和NPT2c,抑制磷重吸收。慢性肾脏病(chronic kidney disease,CKD)患者伴随FGF-23水平升高和α-Klotho蛋白缺乏,FGF-23和α-Klotho蛋白有可能作为CKD预测和早期诊断的生物标志物之一。Fibroblast growth factor 23（ FGF-23） is a central regulator of phosphate metabolism,which can induce phosphaturia by reducing the expression of sodium-dependent phosphate co-transporters（ NPT2 a and NPT2c） in renal proximal tubular cells,can reduce the circulation concentration of 1,25（ OH）2D3by reducing the expression of 1α-hydroxylase（ Cyp27b1） and stimulating the activity of 24-hydroxylase（ Cyp24α1）, can also reduce the secretion of PTH. α-Klotho protein which was first identified as an aging gene is a single-pass transmembrane protein,membrane α-Klotho protein forms a constitutive binary complex with FGF receptors,which enhances FGF and FGFR affinity. Secretedα-Klotho protein has been reported to function as a regulator of phosphate metabolism,independently of FGF-23. In the apical membrane area of the proximal tubule cell, it can promote the absorption of Ca^2＋,can inactivate NPT2 a and NPT2 c,can also inhibit P reabsorption by the modify of xylanase. Patients with chronic kidney disease（ CKD） have the increased levels of FGF-23 and deficiency of α-Klotho protein,FGF-23 and α-Klotho protein play an important role in the CKD associated mineral bone disease（ CKD-MBD）. FGF-23 and α-Klotho protein can be used as the prediction and early diagnosis biomarkers of CKD,and provide a new perspective for the study and treatment of the pathophysiology of CKD.

关 键 词：成纤维细胞生长因子23 α-Klotho蛋白 慢性肾脏病 

分 类 号：R681[医药卫生—骨科学]