ArticleCell death discovery2023
PDK4 rescues high-glucose-induced senescent fibroblasts and promotes diabetic wound healing through enhancing glycolysis and regulating YAP and JNK pathway.
Article in Cell death discovery, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
What it found
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The trial behind it
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Who cites it
42 citing papers in PubMed, 46 citations in OpenAlex.
- Adipose-derived mesenchymal stem cells promote diabetic wound healing through ALDOA secretion.Regenerative therapy · 2026Article
- METTL3 Regulates the Senescence of Stem Cells From the Apical Papilla by Mediating the mInternational dental journal · 2026Article
- In Vitro Evaluation of Novel Synthetic Benzimidazolium-Chalcone Hybrids: Antioxidant and Regenerative Effects in Diabetic Wound Healing.Applied biochemistry and biotechnology · 2026Article
- Intelligent-responsive hydrogel synergistically mediates immune remodel-antibacterial-angiogenesis cascade for diabetic foot ulcer repair.Bioactive materials · 2026Article
- Enhancing pulp regeneration through metabolic reprogramming of mature dental pulp stem cells mediated by GLUT1/HK2 mRNA delivery.International journal of oral science · 2026Article
- [Influence and mechanism of PBNP combined with mouse ADSCs on full-thickness skin defect wounds in diabetic mice].Zhonghua shao shang yu chuang mian xiu fu za zhi · 2026Article
- Single-cell transcriptomic profiling reveals PDK4 upregulation and impaired VEGF-C/VEGFR3 signaling in cardiac lymphatic endothelial cells in diabetic cardiomyopathy.Molecular medicine (Cambridge, Mass.) · 2026Article
- Marine-Derived Polyketides fromACS pharmacology & translational science · 2026Article
- Role of LDHA in senescent fibroblast exosomes promoting ferroptosis via histone lactylation-mediated ACSL4 regulation in skin photoaging.Epigenetics & chromatin · 2026Article
- Hypoxic preconditioning drives metabolic reprogramming to increase the therapeutic efficacy of adipose mesenchymal stem cells in diabetic wounds.Journal of translational medicine · 2026Article
- CD8Science China. Life sciences · 2026Review
- Deuterated polyunsaturated fatty acids alleviate in vitro skeletal muscle dysfunction induced by oxidative stress.Free radical biology & medicine · 2026Article
- Shear-Calibrated High-Intensity Interval Training to Promote Endothelial Autophagy and Delay Vascular Senescence: A Biomarker-Guided Approach.International journal of molecular sciences · 2026Review
- Identification of mitochondrial associated genes as diagnostic biomarkers for basal cell carcinoma: Comprehensive bioinformatics analysis and experimental validation.Glycoconjugate journal · 2026Article
- aFGF rescues high glucose-induced senescent fibroblasts and improves diabetic wound healing by regulating SIRT1/STAT3 pathway.Scientific reports · 2026Article
- The Interplay Between Stiffness and Hyperglycemia on Diabetic Foot Ulcer Wound Closure.Cellular and molecular bioengineering · 2026Article
- Infection-driven proliferative phase impairment in chronic wounds: a mechanistic framework for precision regenerative therapy.Frontiers in immunology · 2026Review
- Metabolic reprogramming in diabetic complications: mechanisms, pathologies, and molecular evidence from multi-organ studies.Frontiers in immunology · 2026Review
- Mechanism of ribonucleic acid-binding protein ILF2 in promoting diabetic foot ulcer wound healing via regulating the nucleophosmin 1/NF-κB axis.Burns & trauma · 2026Article
- Progress on hydrogel delivery systems targeting metabolism disorders in the treatment of diabetic foot ulcers.Frontiers in cell and developmental biology · 2026Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
During the process of wound healing, fibroblasts migrate to the wound site and perform essential functions in promoting cell proliferation, as well as synthesizing and secreting the extracellular matrix (ECM). However, in diabetic wounds, senescent fibroblasts exhibit impaired proliferative capacity and fail to synthesize essential ECM components. Pyruvate dehydrogenase kinase 4 (PDK4), a key enzyme regulating energy metabolism, has been implicated in modulating cellular senescence and fibroblast function. However, its specific role in diabetic wounds remains poorly understood. In this study, we conducted a series of in vivo and in vitro experiments using STZ-induced diabetic mice and human dermal fibroblasts. We evaluated cellular senescence markers, including SA-β-gal, P53, P16, P21, and PAI-1, as well as senescence-associated secretory phenotype (SASP) factors. Finally, we observed that PDK4 increased in normal wound healing, but its expression was insufficient in diabetic wounds. Significantly, the overexpression of PDK4 demonstrated the potential to accelerate diabetic wound healing and improve the senescence phenotype both in vivo and in vitro. Furthermore, our study elucidated the underlying mechanism by which PDK4 improved the senescent phenotype through the enhancement of glycolysis and regulation of YAP and JNK pathway. The effect was dependent on metabolic reprogramming and subsequent reduction of reactive oxygen species (ROS), which was mediated by PDK4. Overall, our findings highlight the potential of PDK4 as a promising therapeutic target for addressing diabetic wounds.
Identifiers
What Socratic holds
Registered trials
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 Socratic graph.