Secreted klotho and chronic kidney disease.

Secreted klotho and chronic kidney disease.
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DOI:
10.1007/978-1-4614-0887-1_9
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发表时间:
2012
影响因子:
--
通讯作者:
Moe, Orson W.
Moe, Orson W.
中科院分区:
医学4区
文献类型:
--
作者:
Hu, Ming Chang;Kuro-o, Makoto;Moe, Orson W.

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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Klotho的胞外区可以从细胞表面的膜锚定Klotho释放出来。与作为成纤维细胞生长因子-23(FGF23)的辅助受体的膜Klotho不同,SKL作为激素因子,在抗衰老、抗氧化、调节离子转运和Wnt信号转导方面发挥重要作用。新的证据显示,Klotho缺乏症是慢性肾脏疾病的早期生物标志物,也是一个致病因素。Klotho缺乏与慢性肾脏疾病的进展和慢性并发症有关,包括血管钙化、心肌肥厚和继发性甲状旁腺功能亢进症。在多个实验模型中,在慢性肾脏疾病中,SKL的替代或操纵内源性Klotho的上调可以保护肾脏免受肾脏损伤,保护肾功能,抑制肾脏纤维化。Klotho作为一种早期生物标志物和一种治疗慢性肾脏疾病的新药物,是一个非常有希望的候选者。
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.
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