ArticlePloS one2021
Protective effects of klotho on palmitate-induced podocyte injury in diabetic nephropathy.
Article in PloS one, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 39 citations in OpenAlex.
- Impact of Uremic Toxins on Endothelial Dysfunction in Chronic Kidney Disease: A Systematic Review.International journal of molecular sciences · 2022Pooled it
- Pharmaceutical Strategies for Translating Klotho-Based Therapeutics: From Biologic Developability to Advanced Delivery Systems.Pharmaceutics · 2026Review
- Targeting cellular senescence in diabetic kidney disease: potential of regenerative, cell-based therapies and other senotherapeutic approaches.Kidney international · 2026Review
- Post‑translational modifications in diabetic kidney disease (Review).International journal of molecular medicine · 2026Review
- Review
- Association between the serum Klotho levels and diabetic kidney disease: results from the NHANES 2007-2016 and Mendelian randomization study.Journal of diabetes and metabolic disorders · 2025Article
- Klotho protein alleviates heart ischemia/reperfusion injury and oxidative stress through regulation of the NOS/MMP pathway.Scientific reports · 2025Article
- Associations of serum Klotho with diabetic kidney disease prevalence and mortality: insights from a nationally representative U.S. cohort.Diabetology & metabolic syndrome · 2025Article
- Klotho antiaging protein: molecular mechanisms and therapeutic potential in diseases.Molecular biomedicine · 2025Review
- Research on podocyte injury mechanisms in diabetic nephropathy: a bibliometric and knowledge-map analysis from 2000 to 2024.Frontiers in endocrinology · 2025Article
- Review
- Non-voltage-gated CaAmerican journal of physiology. Renal physiology · 2024Review
- Mitochondrial metabolic reprogramming in diabetic kidney disease.Cell death & disease · 2024Review
- The interaction between klotho protein and epigenetic alteration in diabetes and treatment options.Journal of diabetes and metabolic disorders · 2024Review
- Cytoskeleton Rearrangement in Podocytopathies: An Update.International journal of molecular sciences · 2024Review
- CD36-mediated podocyte lipotoxicity promotes foot process effacement.Open medicine (Warsaw, Poland) · 2024Article
- Klotho Stabilizes the Podocyte Actin Cytoskeleton in Idiopathic Membranous Nephropathy through Regulating the TRPC6/CatL Pathway.American journal of nephrology · 2024Article
- In vivo safety and biodistribution profile of Klotho-enhanced human urine-derived stem cells for clinical application.Stem cell research & therapy · 2023Article
- Triptolide protects against podocyte injury in diabetic nephropathy by activating the Nrf2/HO-1 pathway and inhibiting the NLRP3 inflammasome pathway.Renal failure · 2023Article
- Soluble Klotho protects against glomerular injury through regulation of ER stress response.Communications biology · 2023Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The anti-aging gene, klotho, has been identified as a multi-functional humoral factor and is implicated in multiple biological processes. However, the effects of klotho on podocyte injury in diabetic nephropathy are poorly understood. Thus, the current study aims to investigate the renoprotective effects of klotho against podocyte injury in diabetic nephropathy. We examined lipid accumulation and klotho expression in the kidneys of diabetic patients and animals. We stimulated cultured mouse podocytes with palmitate to induce lipotoxicity-mediated podocyte injury with or without recombinant klotho. Klotho level was decreased in podocytes of lipid-accumulated obese diabetic kidneys and palmitate-treated mouse podocytes. Palmitate-treated podocytes showed increased apoptosis, intracellular ROS, ER stress, inflammation, and fibrosis, and these were significantly attenuated by klotho administration. Klotho treatment restored palmitate-induced downregulation of the antioxidant molecules, Nrf2, Keap1, and SOD1. Klotho inhibited the phosphorylation of FOXO3a, promoted its nuclear translocation, and then upregulated MnSOD expression. In addition, klotho administration attenuated palmitate-induced cytoskeleton changes, decreased nephrin expression, and increased TRPC6 expression, eventually improving podocyte albumin permeability. These results suggest that klotho administration prevents palmitate-induced functional and morphological podocyte injuries, and this may indicate that klotho is a potential therapeutic agent for the treatment of podocyte injury in obese diabetic nephropathy.
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