Renal Physiology Research Laboratory, Department of Nephrology and Hypertension, Meir Medical Center, Kfar Saba, Israel.
Nephrol Dial Transplant. 2011 Aug;26(8):2433-8. doi: 10.1093/ndt/gfr208. Epub 2011 May 4.
Fibroblast growth factor (FGF) 23 and Klotho are two factors associated with several metabolic disorders. Similar to humans, accelerated aging processes characterized by chronic vascular disease, bone demineralization, skin atrophy and emphysema have been recognized in FGF23-null mice and Klotho-deficient mice. The role of these factors in the control of mineral metabolism homeostasis have been shown recently, particularly at the level of parathyroid cells and also in modulating active vitamin D production, two phenomena which are relevant in the presence of chronic kidney disease. In addition, the hormonal affect of circulating FGF23 and Klotho proteins on vascular reactivity, either directly on endothelial cell functions or indirectly by modulating the brain endothelin-1-dependent sympathetic nervous system activity, has contributed to understanding their role in the pathophysiology of hypertension and atherosclerotic vasculopathies. Consequently, very recent clinical investigations seem to confirm the involvement of Klotho in modulating the severity and prognosis of human cardiovascular (CV) disorders and longevity. The present review reports data related to the possible interactive effects of Klotho and FGF23 on the prognosis of renal and CV diseases.
成纤维细胞生长因子 23(FGF23)和 Klotho 是与多种代谢紊乱相关的两种因子。与人类相似,FGF23 基因敲除小鼠和 Klotho 基因缺陷小鼠表现出加速衰老的过程,其特征为慢性血管疾病、骨矿物质化、皮肤萎缩和肺气肿。这些因子在矿物质代谢稳态控制中的作用最近已经得到证实,特别是在甲状旁腺细胞水平,以及在调节活性维生素 D 产生方面,这两种现象在慢性肾脏病中具有相关性。此外,循环 FGF23 和 Klotho 蛋白对血管反应性的激素影响,无论是直接对内皮细胞功能的影响,还是通过调节脑内皮素-1 依赖性交感神经系统活动的间接影响,都有助于理解它们在高血压和动脉粥样硬化血管病变的病理生理学中的作用。因此,最近的临床研究似乎证实了 Klotho 在调节人类心血管(CV)疾病严重程度和预后以及长寿方面的作用。本综述报告了有关 Klotho 和 FGF23 对肾脏和 CV 疾病预后可能的相互作用的相关数据。