ArticleDiabetology & metabolic syndrome2025
Activation of M1 macrophages promotes diabetic kidney disease by modulating glycolysis via HIF-1α-HK2 signaling pathway.
Article in Diabetology & metabolic syndrome, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.
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Who cites it
12 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
- Hexosamine Biosynthetic Pathway and Fatty Acid β-Oxidative Imbalance: A Key Mechanism by Which Abnormal Macrophage Lipophagy Promotes Atherosclerosis in Diabetes.Cardiovascular drugs and therapy · 2026Review
- Myeloid myeloid PRDM16 restrains macrophage inflammatory remodeling and renal fibrosis in diabetic kidney disease by limiting PI3K/AKT activation.Acta diabetologica · 2026Article
- Association between triglyceride-to-high-density lipoprotein cholesterol ratio and albuminuria in patients with type 2 diabetes: a cross-sectional study.Frontiers in nutrition · 2026Article
- Metabolic reprogramming in diabetic complications: mechanisms, pathologies, and molecular evidence from multi-organ studies.Frontiers in immunology · 2026Review
- Lactate Metabolism and Protein Lactylation in Diabetic Kidney Disease: A Narrative Review.Diabetes, metabolic syndrome and obesity : targets and therapy · 2026Review
- Mechanisms of Macrophage Glycolytic Reprogramming and Interventional Effects of Traditional Chinese Medicine on Renal Fibrosis.International journal of general medicine · 2026Review
- Neoepitopes at the crossroads of immunometabolism: metabolic remodeling of antigen presentation in type 1 diabetes.Frontiers in immunology · 2026Review
- Role of metabolic reprogramming and lactylation in diabetic nephropathy: molecular mechanisms and therapeutic prospects - a narrative review.Frontiers in endocrinology · 2026Review
- Hexokinase 2 upregulation is associated with glycolytic reprogramming and neuroinflammation in hypoxic-ischemic brain damage: a therapeutic target for early intervention.Frontiers in immunology · 2026Article
- Immune-metabolic interactions shape the fibrotic landscape of diabetic kidney disease: emerging mechanisms and therapeutic prospects.Frontiers in physiology · 2025Review
- [Nan fang yi ke da xue xue bao = Journal of Southern Medical UniversityArticle
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Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveMacrophages and glycolysis play a pivotal role in diabetic kidney disease (DKD). However, the regulation of macrophage glycolysis and its mechanism are still unclear in DKD. Thus, this research intends to investigate the regulatory mechanism of macrophage glycolysis during DKD.
methodsMacrophage polarization in patients with DKD and in mice was assessed using RT-qPCR and immunofluorescence. DKD was induced in the mice through injection of streptozotocin, and a high-fat diet was administered. Hematoxylin and eosin staining and Masson's trichrome staining were employed to identify pathological alterations and visualize renal collagen fibers in the model mice. Glycolytic metabolite levels were quantified using a commercially available kit. Protein levels of HK2, PFK1, LDH, PK1, and GLUT1 were analyzed via western blotting. Hkb-20 cells exposed to high glucose were utilized as an in vitro experimental model. THP-1 cells were co-cultivated with Hkb-20 cells. The impact of macrophage polarization on the functionality of Hkb-20 cells was assessed through CCK8 assay, flow cytometry, and wound healing assay. Levels of IL-6, IL-1β, and TNF-α were evaluated using ELISA kits. Immunofluorescence staining was employed to examine the co-localization of hypoxia-inducible factor-1 (HIF-1α) and HK2.
resultsWe found that M1 macrophage polarization and enhanced glycolysis activity emerged in DKD patients and mice. Furthermore, we demonstrated that M1 macrophage polarization promotes glycolysis activity in macrophage and model mice. Moreover, we found that HIF-1α and HK2 were obviously enhanced in the serum of DKD cases and mice. Mechanically, we revealed that HIF-1α participates in M1 macrophage polarization and glycolysis activity in vitro by activating HK2 transcription.
conclusionWe demonstrated that M1 macrophage polarization mediated glycolysis contributed to DKD via regulating HIF-1α-HK2 signaling pathway.
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