ArticleNature communications2025
Branched-chain amino acids contribute to diabetic kidney disease progression via PKM2-mediated podocyte metabolic reprogramming and apoptosis.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it.
- The lactate-lactylation axis in renal fibrosis: potential mechanisms in diabetic kidney disease.Annals of medicine · 2025Pooled it
- Article
- KLF transcription factors in metabolic kidney disease: from podocyte protection to tubulointerstitial fibrosis.International urology and nephrology · 2026Review
- Amino Acid Metabolism in Health and Disease.MedComm · 2026Review
- Metabolomic Profiling Delineates Stage-Associated Metabolic Remodelling in Cardiovascular-Kidney-Metabolic Syndrome.Diabetes/metabolism research and reviews · 2026Article
- Amino acid homeostasis in the kidney: Physiological roles and pathological dysregulation.Physiological reports · 2026Review
- Mitochondrial metabolic reprogramming drives diabetic kidney disease progression: cell-specific mechanisms, metabolic memory, and targeted strategies.Molecular medicine (Cambridge, Mass.) · 2026Review
- REDD1 deficiency alleviates podocyte PANoptosis and restores autophagy in diabetic kidney disease.Molecular medicine (Cambridge, Mass.) · 2026Article
- Multi-Omics and Functional Validation Identify a Quercetin-SLC15A2 Axis That Mediates the Anti-Fibrotic Effect of Shen-Kang Recipe in Diabetic Kidney Disease.International journal of molecular sciences · 2026Article
- Amino acid metabolism in diabetic kidney disease.Clinical and experimental nephrology · 2026Review
- Podocyte Metabolic Reprogramming and Targeted Therapy.Journal of the American Society of Nephrology : JASN · 2026Review
- Targeting the metabolic fingerprint of amino acids to identify novel metabolic characteristics in osteosarcoma patients undergoing anthracycline treatment.Scientific reports · 2026Article
- Untangling amino acid metabolism in renal diseases: mechanisms, dysregulation, and critical gaps.Clinical kidney journal · 2026Review
- Review
- New Insights into the Role of Mitochondrial Dysfunction in Diabetic Kidney Disease in the Omics Era.Diabetes, metabolic syndrome and obesity : targets and therapy · 2026Review
Corrections and comments
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Authors and funding
24 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Approximately 30-40% of patients with diabetes develop diabetic kidney disease (DKD). Identifying decisive factors for DKD initiation is crucial. Here, we observed that glomerular podocytes in male and female patients with DKD and db/db mice specifically displayed BCAA catabolic defects. Podocyte-specific PP2Cm (a key BCAA catabolism enzyme) knockout or exogenous BCAA supplementation induced DKD phenotypes including podocyte dysfunction/apoptosis, glomerular pathology, and proteinuria in high-fat (HF)-diet-fed male mice. Mechanistically, BCAAs promoted PKM2 depolymerization and inactivation in podocytes. Depolymerized PKM2 suppressed glucose oxidative phosphorylation (OXPHOS), diverting glucose metabolism towards serine biosynthesis and folate metabolism. Depolymerized PKM2 is also co-transported with DDIT3 into the nucleus, acting as a co-transcriptional factor to enhance DDIT3 transcriptional activity, which promotes Chac1 and Trib3 expression and directly inducing podocyte apoptosis. Thus, BCAA catabolic defects may be one of the missing factors that determine DKD initiation. Targeting BCAA catabolism or PKM2 activation is a promising DKD prevention strategy.
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