ArticleThe Journal of investigative dermatology2015
Thrombomodulin promotes diabetic wound healing by regulating toll-like receptor 4 expression.
Article in The Journal of investigative dermatology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 26 citations in OpenAlex.
- DLST-driven metabolic alterations link skin to blood glucose: A translational study from mouse to human.Molecular metabolism · 2026Article
- A Narrative Review on Abnormalities in the Hemostatic System in Diabetes Mellitus: Pathophysiology, Clinical Implications, and Therapeutics.Life (Basel, Switzerland) · 2026Review
- Heat stress alters metabolic pathways and nitric oxide signaling in keratinocytes under hyperglycemia.Journal of diabetes investigation · 2026Article
- Synergistic COInternational journal of molecular sciences · 2025Article
- Association of Thrombomodulin Expression with Bladder Cancer Grade, Stage, and Recurrence: A Single-Center Prospective Pilot Study.Iranian journal of pathology · 2025Article
- Investigating Inflammatory Markers in Wound Healing: Understanding Implications and Identifying Artifacts.ACS pharmacology & translational science · 2024Review
- Enhancing wound healing through innovative technologies: microneedle patches and iontophoresis.Frontiers in bioengineering and biotechnology · 2024Article
- The Epidermal Keratinocyte as a Therapeutic Target for Management of Diabetic Wounds.International journal of molecular sciences · 2023Review
- Nanostructured Lipid Carrier Gel Formulation of Recombinant Human Thrombomodulin Improve Diabetic Wound Healing by Topical Administration.Pharmaceutics · 2021Article
- Investigations into Chemical Components fromJournal of fungi (Basel, Switzerland) · 2021Article
- Innate Immunity in Diabetic Wound Healing: Focus on the Mastermind Hidden in Chronic Inflammatory.Frontiers in pharmacology · 2021Review
- Epigenetic Regulation of TLR4 in Diabetic Macrophages Modulates Immunometabolism and Wound Repair.Journal of immunology (Baltimore, Md. : 1950) · 2020Article
- A thrombomodulin-like gene is crucial to the collective migration of epibolic blastomeres during germ layer formation and organogenesis in zebrafish.Journal of biomedical science · 2019Article
- Histone Methylation Directs Myeloid TLR4 Expression and Regulates Wound Healing following Cutaneous Tissue Injury.Journal of immunology (Baltimore, Md. : 1950) · 2019Article
- Plasminogen/thrombomodulin signaling enhances VEGF expression to promote cutaneous wound healing.Journal of molecular medicine (Berlin, Germany) · 2018Article
- Wound healing in Mac-1 deficient mice.Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society · 2017Article
- Gallic Acid Promotes Wound Healing in Normal and Hyperglucidic Conditions.Molecules (Basel, Switzerland) · 2016Article
- Myeloid thrombomodulin lectin-like domain inhibits osteoclastogenesis and inflammatory bone loss.Scientific reports · 2016Article
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Keratinocyte-expressed thrombomodulin (TM) and the released soluble TM (sTM) have been demonstrated to promote wound healing. However, the effects of high glucose on TM expression in keratinocytes and the role of TM in diabetic ulcer remain unclear. In this study, we demonstrated that expressions of TM and Toll-like receptor 4 (TLR4) were both downregulated in high-glucose cultured human keratinocytes and in skin keratinocytes of diabetic patients. In addition, the wound-triggered upregulation of TM and sTM production was abolished in both high-glucose cultured human keratinocytes and streptozotocin-induced diabetic mouse skin. Furthermore, supplementation of recombinant sTM could increase TLR4 expression and promote cutaneous wound healing in both high-glucose cultured human keratinocytes and diabetic mice. However, in Tlr4-deleted mice, which exhibited delayed wound healing, the therapeutic benefit of recombinant sTM was abrogated. Moreover, our results showed that tumor necrosis factor-α (TNF-α) expression in keratinocytes was dose-dependently upregulated by glucose, and TNF-α treatment downregulated the expression of TM and TLR4. Taken together, high-glucose environment reduces the expression of TM and TLR4 in keratinocytes possibly through the action of TNF-α, and recombinant sTM can increase the TLR4 expression and promote wound healing under diabetic condition.
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