Klotho antiaging protein: molecular mechanisms and therapeutic potential in diseases.

IF 6.3 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Aditya Dipakrao Hajare, Neha Dagar, Anil Bhanudas Gaikwad
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Abstract

Klotho, initially introduced as an anti-aging protein, is expressed in the brain, pancreas, and most prominently in the kidney. The two forms of Klotho (membrane-bound and soluble form) have diverse pharmacological functions such as anti-inflammatory, anti-oxidative, anti-fibrotic, tumour-suppressive etc. The membrane-bound form plays a pivotal role in maintaining kidney homeostasis by regulating fibroblast growth factor 23 (FGF 23) signalling, vitamin D metabolism and phosphate balance. Klotho deficiency has been linked with significantly reduced protection against various kidney pathological phenotypes, including diabetic kidney disease (DKD), which is a major cause of chronic kidney disease leading to end-stage kidney disease. Owing to the pleiotropic actions of klotho, it has shown beneficial effects in DKD by tackling the complex pathophysiology and reducing kidney inflammation, oxidative stress, as well as fibrosis. Moreover, the protective effect of klotho extends beyond DKD in other pathological conditions, including cardiovascular diseases, alzheimer's disease, cancer, inflammatory bowel disease, and liver disease. Therefore, this review summarizes the relationship between Klotho expression and various diseases with a special emphasis on DKD, the distinct mechanisms and the potential of exogenous Klotho supplementation as a therapeutic strategy. Future research into exogenous Klotho could unravel novel treatment avenues for DKD and other diseases.

Klotho抗衰老蛋白:分子机制及其在疾病中的治疗潜力。
Klotho最初是作为一种抗衰老蛋白引入的,在大脑、胰腺和肾脏中都有表达。两种形式的Klotho(膜结合形式和可溶性形式)具有不同的药理功能,如抗炎、抗氧化、抗纤维化、抑制肿瘤等。这种膜结合形式通过调节成纤维细胞生长因子23 (FGF 23)信号、维生素D代谢和磷酸盐平衡,在维持肾脏稳态中起关键作用。Klotho缺乏与各种肾脏病理表型的保护能力显著降低有关,包括糖尿病肾病(DKD),这是导致终末期肾脏疾病的慢性肾脏疾病的主要原因。由于klotho的多效性,它通过解决复杂的病理生理和减轻肾脏炎症、氧化应激和纤维化,在DKD中显示出有益的作用。此外,klotho的保护作用超出了DKD对其他病理疾病的保护作用,包括心血管疾病、阿尔茨海默病、癌症、炎症性肠病和肝病。因此,本文综述了Klotho表达与各种疾病的关系,特别强调了DKD、不同的机制和外源性补充Klotho作为治疗策略的潜力。未来对外源性Klotho的研究可能会为DKD和其他疾病的治疗开辟新的途径。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
6.30
自引率
0.00%
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0
审稿时长
10 weeks
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