ArticleJCI insight2022
Regeneration of glomerular metabolism and function by podocyte pyruvate kinase M2 in diabetic nephropathy.
Article in JCI insight, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 42 citations in OpenAlex.
- Cell-type-specific damage scores reveal kidney and liver disease trajectories in single-cell and spatial transcriptomics.Cell genomics · 2026Article
- Arachidonic Acid Disrupts PKM2-Linked Glycolysis-Related Metabolism and Exacerbates PAN-Induced Podocyte Injury.Journal of cellular and molecular medicine · 2026Article
- Metabolic determinants of autoimmune kidney diseases.Nature reviews. Nephrology · 2026Review
- The Role of Glycolysis in Diabetic Kidney Disease.International journal of molecular sciences · 2026Review
- Article
- Podocyte Metabolic Reprogramming and Targeted Therapy.Journal of the American Society of Nephrology : JASN · 2026Review
- Metabolic Reprogramming and Immunometabolic Dysregulation in Diabetic Kidney Disease: From Pathogenesis to Precision Multi-target Therapies.Research (Washington, D.C.) · 2026Review
- From Wild Vegetable to Renal Protector: The Therapeutic Potential ofFood science & nutrition · 2025Article
- Loss of glomerular aldolase B in diabetic nephropathy promotes renal fibrosis via activating Akt/GSK/β-catenin axis.Journal of advanced research · 2025Article
- Mechanisms and Therapeutic Perspectives of Podocyte Aging in Podocytopathies.International journal of molecular sciences · 2025Review
- The Life of a Kidney Podocyte.Acta physiologica (Oxford, England) · 2025Review
- Glomerular Haematopoietic Prostaglandin D Synthase-Prostaglandin D2 Axis Contributes to the Periodontitis-Related Exacerbation of Diabetic Nephropathy in KK-AJournal of clinical periodontology · 2025Article
- Pyruvate kinase M2 activation maintains mitochondrial metabolism by regulating the interaction between HIF-1α and PGC-1α in diabetic kidney disease.Molecular medicine (Cambridge, Mass.) · 2025Article
- The intelligent podocyte: sensing and responding to a complex microenvironment.Nature reviews. Nephrology · 2025Review
- Differential Effects of Retinol-Binding Protein 3 and Anti-VEGF Antibodies on Retinal Dysfunctions in Diabetic Retinopathy.Diabetes · 2025Article
- The PKM2 activator TEPP-46 suppresses cellular senescence in hydrogen peroxide-induced proximal tubular cells and kidney fibrosis in CD-1Journal of diabetes investigation · 2025Article
- Investigating the role of gut microbiota in diabetic nephropathy through plasma proteome mediated analysis.Scientific reports · 2025Article
- Metabolism at the crossroads of inflammation and fibrosis in chronic kidney disease.Nature reviews. Nephrology · 2025Review
- Podocyte SIRPα reduction in diabetic nephropathy aggravates podocyte injury by promoting pyruvate kinase M2 nuclear translocation.Redox biology · 2024Article
- Spinster homolog 2 (SPNS2) deficiency drives endothelial cell senescence and vascular aging via promoting pyruvate metabolism mediated mitochondrial dysfunction.Cell communication and signaling : CCS · 2024Article
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
Diabetic nephropathy (DN) arises from systemic and local changes in glucose metabolism and hemodynamics. We have reported that many glycolytic and mitochondrial enzymes, such as pyruvate kinase M2 (PKM2), were elevated in renal glomeruli of DN-protected patients with type 1 and type 2 diabetes. Here, mice with PKM2 overexpression specifically in podocytes (PPKM2Tg) were generated to uncover the renal protective function of PPKM2Tg as a potential therapeutic target that prevented elevated albumin/creatinine ratio (ACR), mesangial expansion, basement membrane thickness, and podocyte foot process effacement after 7 months of streptozotocin-induced (STZ-induced) diabetes. Furthermore, diabetes-induced impairments of glycolytic rate and mitochondrial function were normalized in diabetic PPKM2Tg glomeruli, in concordance with elevated Ppargc1a and Vegf expressions. Restored VEGF expression improved glomerular maximal mitochondrial function in diabetic PPKM2Tg and WT mice. Elevated VEGF levels were observed in the glomeruli of DN-protected patients with chronic type 1 diabetes and clinically correlated with estimated glomerular filtration (GFR) - but not glycemic control. Mechanistically, the preservations of mitochondrial function and VEGF expression were dependent on tetrameric structure and enzymatic activities of PKM2 in podocytes. These findings demonstrate that PKM2 structure and enzymatic activation in podocytes can preserve the entire glomerular mitochondrial function against toxicity of hyperglycemia via paracrine factors such as VEGF and prevent DN progression.
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