ArticleUrolithiasis2025
Klotho alleviates oxidative stress and mitochondrial dysfunction through the Nrf2/HO-1 pathway, thereby reducing renal senescence induced by calcium oxalate crystals.
Article in Urolithiasis, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- Klotho-Derived Peptide 1 Protects against Acute Kidney Injury by Directly Targeting Mitochondrial ATAD3A.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Chlorogenic acid mitigates calcium oxalate monohydrate crystal-induced epithelial-to-mesenchymal transition in renal epithelial cells via suppression of HSP60 expression and p38 signaling.Cellular & molecular biology letters · 2026Article
- Antiaging Properties of the Klotho Protein.Cells · 2026Review
- Fetuin-A and Heme Oxygenase 1 as Potential New Markers in the Diagnosis of Diabetic Kidney Disease.International journal of molecular sciences · 2025Review
- Targeting α‑Klotho Protein by Agmatine and Pioglitazone Is a New Avenue against Diabetic Nephropathy.ACS pharmacology & translational science · 2025Article
- Oxidative stress, inflammation and kidney stones.Urolithiasis · 2025Article
- Klotho mitigates diquat-induced myocardial injury in rats by activating Nrf2/ARE-mediated suppression of oxidative stress.American journal of translational research · 2025Article
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Authors and funding
6 authors.
Funding
Abstract
Klotho is an antiaging protein that is primarily secreted by the kidneys. This study aimed to explore the protective effects of Klotho against calcium oxalate (CaOx) crystal-induced renal aging and the underlying mechanisms involved. We established a mouse model of CaOx crystal deposition via the intraperitoneal injection of glyoxylate (Gly) and constructed an in vitro model by stimulating HK2 cells with calcium oxalate monohydrate (COM). Renal aging levels were assessed through β-galactosidase (SA-β-gal) staining and the detection of senescence-associated markers. By overexpressing Klotho both in vitro and in vivo, we examined oxidative stress, mitochondrial function, and renal aging levels. We then evaluated the role of Nrf2/HO-1 signalling pathway-mediated oxidative stress in CaOx crystal-induced renal aging by applying the oxidative stress scavenger N-acetylcysteine (NAC) and overexpressing or inhibiting Nrf2 in HK2 cells. We subsequently overexpressed Klotho while inhibiting Nrf2 to confirm that Klotho exerts its protective effects through the Nrf2/HO-1 pathway. Finally, we measured the methylation levels of the Klotho promoter and assessed the degree of renal aging induced by CaOx crystals after the inhibition of Klotho DNA methylation. We found that the overexpression of Klotho alleviated CaOx crystal-induced oxidative stress and mitochondrial dysfunction, thereby reducing renal aging. NAC mitigated CaOx crystal-induced renal aging. The overexpression of Nrf2 alleviated CaOx crystal-induced oxidative stress and mitochondrial dysfunction, thus reducing renal aging, whereas the knockdown of Nrf2 exacerbated CaOx crystal-induced oxidative stress and mitochondrial dysfunction, leading to more severe renal aging. The combination of Klotho overexpression and Nrf2 knockdown reversed the protective effects of Klotho. CaOx crystals induced an increase in the DNA methylation levels of Klotho in the kidneys, and the inhibition of DNA methylation alleviated CaOx-induced renal aging. This study revealed that Klotho plays a crucial role in calcium oxalate crystal-induced kidney senescence by influencing kidney oxidative stress and mitochondrial function through the Nrf2/HO-1 pathway.
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