ArticleClinical and experimental nephrology2016
Klotho attenuates renal hypertrophy and glomerular injury in Ins2Akita diabetic mice.
Article in Clinical and experimental nephrology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.
- Relationship of Soluble Klotho and Early Stage of Diabetic Nephropathy: A Systematic Review and Meta-Analysis.Frontiers in endocrinology · 2022Pooled it
- DNMT inhibitor ameliorates hyperglycemia and renal inflammation partially via reversing hypermethylation-induced Klotho suppression in diabetic mice.Clinical epigenetics · 2026Article
- 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
- Involvement of ADAM17-Klotho Crosstalk in High Glucose-Induced Alterations of Podocyte Function.International journal of molecular sciences · 2025Article
- Klotho in diabetes mellitus: research progress and clinical implications.Frontiers in endocrinology · 2025Review
- Systemic immunoinflammatory indexes in albuminuric adults are negatively associated with α-klotho: evidence from NHANES 2007-2016.Renal failure · 2024Article
- Early diabetic kidney disease: Focus on the glycocalyx.World journal of diabetes · 2023Review
- Soluble Klotho protects against glomerular injury through regulation of ER stress response.Communications biology · 2023Article
- Association between Serum Soluble α-Klotho and Urinary Albumin Excretion in Middle-Aged and Older US Adults: NHANES 2007-2016.Journal of clinical medicine · 2023Article
- Peroxisome Proliferator-Activated Receptor Gene Knockout Promotes Podocyte Injury in Diabetic Mice.BioMed research international · 2022Article
- Administration of α-Klotho Does Not Rescue Renal Anemia in Mice.Frontiers in pediatrics · 2022Article
- Non-purine selective xanthine oxidase inhibitor ameliorates glomerular endothelial injury in InsAmerican journal of physiology. Renal physiology · 2020Article
- EGCG Attenuates Renal Damage via Reversing Klotho Hypermethylation in Diabetic db/db Mice and HK-2 Cells.Oxidative medicine and cellular longevity · 2020Article
- Accelerated Kidney Aging in Diabetes Mellitus.Oxidative medicine and cellular longevity · 2020Review
- Klotho protein supplementation reduces blood pressure and renal hypertrophy in db/db mice, a model of type 2 diabetes.Acta physiologica (Oxford, England) · 2019Article
- Endothelial Glycocalyx as a Shield Against Diabetic Vascular Complications: Involvement of Hyaluronan and Hyaluronidases.Arteriosclerosis, thrombosis, and vascular biology · 2018Review
- α-klotho and anemia in patients with chronic kidney disease patients: A new perspective.Experimental and therapeutic medicine · 2017Article
- Perturbations of the anti-ageing hormone Klotho in patients with type 1 diabetes and microalbuminuria.Diabetologia · 2017Article
- Article
- Klotho, the Holy Grail of the kidney: from salt sensitivity to chronic kidney disease.International urology and nephrology · 2016Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundExpression of klotho, the renoprotective anti-aging gene, is decreased in diabetic model kidneys. We hypothesized that klotho protein attenuates renal hypertrophy and glomerular injury in a mouse model of diabetic nephropathy.
methodsKlotho transgenic (KLTG) mice were crossed with spontaneously diabetic Ins2Akita (AKITA) mice. Glomerular morphology, macrophage infiltration, urinary albumin excretion and urinary 8-hydroxy-2-deoxy guanosine excretion were examined. In vitro, human glomerular endothelial cells were stimulated with high glucose with or without recombinant klotho, and calpain activity and proinflammatory cytokine expressions were measured.
resultsWe found that klotho protein overexpression attenuates renal hypertrophy and glomerular injury in this mouse model of diabetic nephropathy. Klotho overexpression attenuated renal hypertrophy, albuminuria, glomerular mesangial expansion, and endothelial glycocalyx loss in the AKITA mice. AKITA mice exhibit high levels of urinary 8-hydroxy-2-deoxy guanosine excretion. In the presence of klotho overexpression, this effect was reversed. In addition, the glomerular macrophage infiltration characteristic of AKITA mice was attenuated in KLTG-AKITA mice. In human glomerular endothelial cells, high glucose induced calpain activity. This effect was suppressed by expression of recombinant klotho, which also suppressed the induction of proinflammatory cytokines.
conclusionOur data suggest klotho protein protects against diabetic nephropathy through multiple pathways.
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