1. Aging-related renal injury and inflammation are associated with downregulation of Klotho and induction of RIG-I/NF-κB signaling pathway in senescence-accelerated mice.
- Author
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Zeng Y, Wang PH, Zhang M, and Du JR
- Subjects
- Animals, DEAD Box Protein 58, Down-Regulation, Female, Klotho Proteins, Male, Mice, Signal Transduction physiology, Aging metabolism, DEAD-box RNA Helicases metabolism, Glucuronidase metabolism, Inflammation etiology, Inflammation metabolism, Inflammation pathology, NF-kappa B p50 Subunit metabolism, Renal Insufficiency etiology, Renal Insufficiency metabolism, Renal Insufficiency pathology
- Abstract
Background and Aims: The predominant distribution of the antiaging Klotho protein in both the kidneys and brain may point to its essential role in protecting against dysfunction of the kidney-brain axis during the aging process. Our previous study showed that the downregulation of Klotho was involved in aging-related cognitive impairment in aged senescence-accelerated mouse prone-8 (SAMP8) mice. The present study investigated the potential role of Klotho in aging-associated inflammation and renal injury., Methods: Age- and gender-matched groups of SAMP8 mice and their corresponding normal control senescence-accelerated mouse resistant-1 (SAMR1) were used to investigate the potential role of Klotho in aging-associated inflammation and renal injury., Results: Compared with aged SAMR1 controls, early-stage chronic kidney disease (CKD), which is associated with an increase in the urinary albumin-to-creatinine ratio, inflammatory cell infiltration, glomerulosclerosis, and tubulointerstitial fibrosis, was observed in aged SAMP8 mice. Furthermore, the aging-related loss of Klotho-induced activation of the retinoic acid-inducible gene 1/nuclear factor-κB (RIG-I/NF-κB) signaling pathway and subsequent production of the proinflammatory mediators tumor necrosis factor α, interleukin-6, and inducible nitric oxide synthase in the kidneys of aged SAMP8 mice compared with SAMR1 controls., Conclusions: The present results suggest that aging-related inflammation and the development of early-stage CKD are likely associated with the downregulation of Klotho and induction of the RIG-I/NF-κB signaling pathway in 12-month-old SAMP8 mice. Moreover, aged SAMP8 mice with cognitive deficits and renal damage may be a potential mouse model for investigating the kidney-brain axis in the aging process.
- Published
- 2016
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