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Published on: June 9, 2017

Klotho alleviates oxidative stress and mitochondrial dysfunction through the Nrf2/HO-1 pathway, thereby reducing

Yuexian Xu1,2,3, Jianmin You1,2,3, Junfeng Yao1,2,3

  • 1Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.

Urolithiasis
|March 29, 2025
PubMed

Insights

Klotho protein protects kidneys from aging caused by calcium oxalate crystals by reducing oxidative stress and improving mitochondrial function via the Nrf2/HO-1 pathway.

Area of Science:

  • Nephrology
  • Gerontology
  • Molecular Biology

Background:

  • Klotho is an antiaging protein primarily secreted by the kidneys.
  • Calcium oxalate (CaOx) crystals can induce kidney aging.
  • The protective mechanisms of Klotho against CaOx-induced renal aging require further elucidation.

Purpose of the Study:

  • To investigate the protective effects of Klotho against CaOx crystal-induced renal aging.
  • To explore the underlying mechanisms involving oxidative stress, mitochondrial function, and the Nrf2/HO-1 pathway.
  • To examine the role of Klotho DNA methylation in CaOx-induced kidney aging.

Main Methods:

  • Established mouse and HK2 cell models of CaOx crystal deposition.
  • Overexpressed Klotho in vitro and in vivo.
  • Assessed renal aging markers, oxidative stress, and mitochondrial function.
  • Utilized N-acetylcysteine (NAC), Nrf2 overexpression/knockdown, and Klotho promoter methylation analysis.

Main Results:

  • Klotho overexpression alleviated CaOx-induced oxidative stress, mitochondrial dysfunction, and renal aging.
  • Nrf2/HO-1 pathway activation, mediated by Klotho, was crucial for these protective effects.
  • CaOx crystals increased Klotho DNA methylation, and its inhibition reduced renal aging.

Conclusions:

  • Klotho exerts protective effects against CaOx crystal-induced kidney aging.
  • These effects are mediated through the Nrf2/HO-1 pathway, impacting oxidative stress and mitochondrial function.
  • Modulating Klotho expression and DNA methylation represents a potential therapeutic strategy for CaOx crystal-induced kidney aging.
Keywords:
Kidney stonesKlothoMitochondrial dysfunctionOxidative stressRenal senescence

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