Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Adv Exp Med Biol. 2012;728:126-57. doi: 10.1007/978-1-4614-0887-1_9.
Soluble Klotho (sKl) in the circulation can be generated directly by alterative splicing of the Klotho transcript or the extracellular domain of membrane Klotho can be released from membrane-anchored Klotho on the cell surface. Unlike membrane Klotho which functions as a coreceptor for fibroblast growth factor-23 (FGF23), sKl, acts as hormonal factor and plays important roles in anti-aging, anti-oxidation, modulation of ion transport, and Wnt signaling. Emerging evidence reveals that Klotho deficiency is an early biomarker for chronic kidney diseases as well as a pathogenic factor. Klotho deficiency is associated with progression and chronic complications in chronic kidney disease including vascular calcification, cardiac hypertrophy, and secondary hyperparathyroidism. In multiple experimental models, replacement of sKl, or manipulated up-regulation of endogenous Klotho protect the kidney from renal insults, preserve kidney function, and suppress renal fibrosis, in chronic kidney disease. Klotho is a highly promising candidate on the horizon as an early biomarker, and as a novel therapeutic agent for chronic kidney disease.
循环中的可溶性 Klotho（sKl）可以通过 Klotho 转录本的选择性剪接直接产生，或者膜结合 Klotho 的细胞外结构域可以从细胞膜锚定的 Klotho 上释放。与作为成纤维细胞生长因子 23（FGF23）的核心受体发挥作用的膜结合 Klotho 不同，sKl 作为一种激素因子，在抗衰老、抗氧化、离子转运调节和 Wnt 信号传导中发挥重要作用。新出现的证据表明，Klotho 缺乏是慢性肾脏病的早期生物标志物，也是致病因素。Klotho 缺乏与慢性肾脏病的进展和慢性并发症有关，包括血管钙化、心脏肥大和继发性甲状旁腺功能亢进。在多种实验模型中，sKl 的替代或内源性 Klotho 的操纵上调可保护肾脏免受肾损伤，维持肾功能，并抑制慢性肾脏病中的肾纤维化。Klotho 作为一种很有前途的候选物，有望成为早期生物标志物和慢性肾脏病的新型治疗药物。
