αKlotho and Chronic Kidney Disease.
αKlotho and Chronic Kidney Disease.
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DOI：
10.1016/bs.vh.2016.02.007
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发表时间：
2016
影响因子：
--
通讯作者：
Hu MC
中科院分区：
文献类型：
--
作者：
Neyra JA;Hu MC
α-Klotho（αKlotho）蛋白由Klotho基因编码，作为内分泌成纤维细胞生长因子-23的辅助受体发挥作用。αKlotho的细胞外结构域被分泌酶切割并释放到循环中，称为可溶性αKlotho。循环中的可溶性αKlotho在慢性肾病（CKD）2期开始下降，尿αKlotho在更早的CKD 1期开始下降。因此，可溶性αKlotho是肾功能下降的早期敏感标志物。大量动物实验的临床前数据支持αKlotho缺乏症是CKD进展和肾外CKD并发症（包括心脏和血管疾病、甲状旁腺功能亢进和矿物质代谢紊乱）的致病因素。αKlotho缺陷诱导细胞衰老，并使细胞对各种细胞损伤（包括氧化应激）诱导的细胞凋亡敏感。αKlotho缺乏症还导致自噬和血管生成缺陷，并促进肾脏和心脏的纤维化。最重要的是，预防αKlotho下降、上调内源性αKlotho产生或直接补充可溶性αKlotho均与减轻肾脏纤维化、延缓CKD进展、改善矿物质代谢、改善心脏功能和形态测定以及缓解CKD中的血管钙化相关。因此，在啮齿类动物中，αKlotho不仅是CKD的诊断和预后标志物，而且内源性αKlotho的增强或外源性αKlotho的补充是预防、延缓和降低CKD合并症负荷的有前景的治疗策略。
Alpha-Klotho (αKlotho) protein is encoded by the gene, Klotho, and functions as a coreceptor for endocrine fibroblast growth factor-23. The extracellular domain of αKlotho is cleaved by secretases and released into the circulation where it is called soluble αKlotho. Soluble αKlotho in the circulation starts to decline in chronic kidney disease (CKD) stage 2 and urinary αKlotho in even earlier CKD stage 1. Therefore soluble αKlotho is an early and sensitive marker of decline in kidney function. Preclinical data from numerous animal experiments support αKlotho deficiency as a pathogenic factor for CKD progression and extrarenal CKD complications including cardiac and vascular disease, hyperparathyroidism, and disturbed mineral metabolism. αKlotho deficiency induces cell senescence and renders cells susceptible to apoptosis induced by a variety of cellular insults including oxidative stress. αKlotho deficiency also leads to defective autophagy and angiogenesis and promotes fibrosis in the kidney and heart. Most importantly, prevention of αKlotho decline, upregulation of endogenous αKlotho production, or direct supplementation of soluble αKlotho are all associated with attenuation of renal fibrosis, retardation of CKD progression, improvement of mineral metabolism, amelioration of cardiac function and morphometry, and alleviation of vascular calcification in CKD. Therefore in rodents, αKlotho is not only a diagnostic and prognostic marker for CKD but the enhancement of endogenous or supplement of exogenous αKlotho are promising therapeutic strategies to prevent, retard, and decrease the comorbidity burden of CKD.
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影响因子：
3.6
作者：
Bian A;Neyra JA;Zhan M;Hu MC
通讯作者：
Hu MC
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影响因子：
5.4
作者：
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影响因子：
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作者：
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19.6
作者：
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影响因子：
3.3
作者：
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