ABI3BP promotes renal aging through Klotho-mediated ferroptosis

• Published in: Journal of translational medicine Vol. 22; no. 1; pp. 514 - 12
• Main Authors: Ji, Ren, Wei, Lin, Zan, Yuxin, Li, Xiao, Ma, Shinan, Ma, Liming, He, Xiju, Wang, Li, Ding, Yan
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 29.05.2024; BioMed Central; BMC
• Subjects: ABI3BP; Aging - metabolism; Animals; Apoptosis; Binding proteins; Carrier Proteins - genetics; Carrier Proteins - metabolism; Cell Line; Chronic kidney failure; Enzymes; Ferroptosis; Glucuronidase - metabolism; Humans; Kidney - metabolism; Kidney - pathology; Kidneys; Klotho; Klotho Proteins - metabolism; Male; Methods; Mice; Mice, Inbred C57BL; Mice, Knockout; Physiological aspects; Radiation; Renal aging; China; Ferroptosis; Klotho; Renal aging; ABI3BP
• ISSN: 1479-5876; 1479-5876
• DOI: 10.1186/s12967-024-05300-w

The aging process of the kidneys is accompanied with several structural diseases. Abnormal fiber formation disrupts the balance of kidney structure and function, causing to end-stage renal disease and subsequent renal failure. Despite this, the precise mechanism underlying renal damage in aging remains elusive. In this study, ABI3BP gene knockout mice were used to investigate the role of ABI3BP in renal aging induced by irradiation. The results revealed a significant increase in ABI3BP expression in HK2 cells and kidney tissue of aging mice, with ABI3BP gene knockout demonstrating a mitigating effect on radiation-induced cell aging. Furthermore, the study observed a marked decrease in Klotho levels and an increase in ferroptosis in renal tissue and HK2 cells following irradiation. Notably, ABI3BP gene knockout not only elevated Klotho expression but also reduced ferroptosis levels. A significant negative correlation between ABI3BP and Klotho was established. Further experiments demonstrated that Klotho knockdown alleviated the aging inhibition caused by ABI3BP downregulation. This study identifies the upregulation of ABI3BP in aged renal tubular epithelial cells, indicating a role in promoting ferroptosis and inducing renal aging by inhibiting Klotho expression.