ArticleDiabetologia2024
ACSF2 and lysine lactylation contribute to renal tubule injury in diabetes.
Article in Diabetologia, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 1 of them a synthesis that pooled it.
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Who cites it
57 citing papers in PubMed, 1 synthesis or guideline pooled it, 47 citations in OpenAlex.
- The lactate-lactylation axis in renal fibrosis: potential mechanisms in diabetic kidney disease.Annals of medicine · 2025Pooled it
- Metabolic memory in the kidney: how lactate and lactylation drive the path from acute injury to chronic disease.Renal failure · 2026Review
- Targeting mitochondrial quality control in diabetic kidney disease: emerging therapeutic opportunities.Renal failure · 2026Review
- Advancements in early biomarkers of acute kidney injury: from traditional indicators to a paradigm shift in lactate metabolism.Annals of medicine · 2026Review
- Epigenetically silencing gluconeogenic enzyme PCK1 by EZH2 promotes renal tubulointerstitial fibrosis.Molecular biomedicine · 2026Article
- Sodium Butyrate Attenuates Renal Fibrosis by Regulating Glycolysis and Histone H4K12 Lactylation in Diabetic Kidney Disease.Diabetes, obesity & metabolism · 2026Article
- Lactate-Mediated Lysine Lactylation in Renal Fibrosis: Current Progress and Challenges.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Review
- The Lactate-lactylation circuitry in kidney fibrosis: cellular crosstalk from tubular metabolic reprogramming to macrophage effector functions.Seminars in immunopathology · 2026Review
- Amino acid homeostasis in the kidney: Physiological roles and pathological dysregulation.Physiological reports · 2026Review
- Lysine l-Lactylation: Bridging Metabolism, Chromatin and Disease.Cell proliferation · 2026Review
- Lactylation modification: a new bridge connecting macrophage metabolism and pulmonary hypertension.Applied microbiology and biotechnology · 2026Review
- Article
- Targeting posttranslational modifications of oxidative stress pathways for the treatment of diabetic nephropathy.Journal of pharmaceutical analysis · 2026Review
- Glycolytic lactylation modulates cell death decisions in diabetic kidney disease: Metabolic‑epigenetic interplay between ferroptosis and autophagy in fibrotic remodeling (Review).International journal of molecular medicine · 2026Review
- Unveiling lactylation: A novel frontier in the pathogenesis of diabetic nephropathy (Review).International journal of molecular medicine · 2026Review
- Keratin 18 functions as a lactyltransferase to trigger necroptosis in diabetic kidney disease by modulating Fas transcription.Experimental & molecular medicine · 2026Article
- Lactate and lactylation: mechanisms, function, diseases, and therapeutic targets.Molecular biomedicine · 2026Review
- Article
- Role and clinical importance of lactylation in tumors (Review).Molecular medicine reports · 2026Review
- Identification and validation of lactylation-related diagnostic biomarkers for type 2 diabetes by WGCNA.Journal of clinical biochemistry and nutrition · 2026Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
aimsLactate accumulation is reported to be a biomarker for diabetic nephropathy progression. Lactate drives lysine lactylation, a newly discovered post-translational modification that is involved in the pathogenesis of cancers and metabolic and inflammatory disease. Here, we aimed to determine whether lysine lactylation is involved in the pathogenesis of diabetic nephropathy.
methodsRenal biopsy samples from individuals with diabetic nephropathy (n=22) and control samples from individuals without diabetes and kidney disease (n=9) were obtained from the First Affiliated Hospital of Zhengzhou University for immunohistochemical staining. In addition, we carried out global lactylome profiling of kidney tissues from db/m and db/db mice using LC-MS/MS. Furthermore, we assessed the role of lysine lactylation and acyl-CoA synthetase family member 2 (ACSF2) in mitochondrial function in human proximal tubular epithelial cells (HK-2).
resultsThe expression level of lysine lactylation was significantly increased in the kidneys of individuals with diabetes as well as in kidneys from db/db mice. Integrative lactylome analysis of the kidneys of db/db and db/m mice identified 165 upregulated proteins and 17 downregulated proteins, with an increase in 356 lysine lactylation sites and a decrease in 22 lysine lactylation sites decreased. Subcellular localisation analysis revealed that most lactylated proteins were found in the mitochondria (115 proteins, 269 sites). We further found that lactylation of the K182 site in ACSF2 contributes to mitochondrial dysfunction. Finally, the expression of ACSF2 was notably increased in the kidneys of db/db mice and individuals with diabetic nephropathy.
conclusionsOur study strongly suggests that lysine lactylation and ACSF2 are mediators of mitochondrial dysfunction and may contribute to the progression of diabetic nephropathy. DATA AVAILABILITY: The LC-MS/MS proteomics data have been deposited in the ProteomeXchange Consortium database ( https://proteomecentral.proteomexchange.org ) via the iProX partner repository with the dataset identifier PXD050070.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.