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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

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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.

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Acknowledgments

This work was supported by the National Science Foundation of China (81473219).

Conflict of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

Human and Animal Rights

All of the animal procedures were performed according to China Animal Welfare Legislation and the Guidelines of Laboratory Animal Care and Use of Sichuan University.

Informed consent

All participants signed an informed consent form prior to their inclusion in the study.

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Correspondence to Jun-Rong Du.

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40520_2015_371_MOESM1_ESM.tif

Supplementary material 1 (TIFF 39728 kb) Fig. S1. Immunohistochemical staining of renal Klotho expression in C57BL/6 mice. Representative images show Klotho immunoreactivity in the renal cortex and medulla in 15-week-old male C57BL/6 mice

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Zeng, Y., Wang, PH., Zhang, M. et al. 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. Aging Clin Exp Res 28, 69–76 (2016). https://doi.org/10.1007/s40520-015-0371-y

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  • DOI: https://doi.org/10.1007/s40520-015-0371-y

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