ArticleJournal of neuroinflammation2020
Thrombomodulin facilitates peripheral nerve regeneration through regulating M1/M2 switching.
Article in Journal of neuroinflammation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 62 citations in OpenAlex.
- A multifunctional ZIF-8@CuO/collagen-binding peptide hydrogel for photothermal-enhanced antibacterial and infected skin wound management.RSC advances · 2026Article
- Decellularized matrix grafts and peripheral nerve regeneration.Neural regeneration research · 2026Article
- Islets co-engineered with thrombomodulin and CD47 achieve sustained survival in allogeneic recipients without chronic immunosuppression.JCI insight · 2026Article
- Injectable anti-inflammatory, antioxidant supramolecular nanofiber hydrogel for peripheral nerve injury repair and neuropathic pain relief.Materials today. Bio · 2026Article
- Balancing inflammation and regeneration: immune cell dynamics in nerve repair: a comprehensive review.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
- Dose-optimized HILT promotes peripheral nerve repair through BMP4-Smad9-mediated inhibition of neuroinflammation and oxidative stress.APL bioengineering · 2026Article
- Nerve Injury-Induced Immune Responses in the Taste Bud Target Field.International journal of molecular sciences · 2026Article
- M2 polarization of macrophage induced by IL-33 promotes mouse sciatic nerve regeneration.Cell & bioscience · 2026Article
- Association between pre-diagnostic prevalence of 30 common diseases and the subsequent risk of dementia: a population-based retrospective cohort study in Taiwan.Frontiers in aging neuroscience · 2026Article
- Recent Advances in Silk Fibroin Derived fromJournal of functional biomaterials · 2025Review
- Research progress of platelet-rich plasma in promoting peripheral nerve repair.Neurogenetics · 2025Review
- The Dance Between Schwann Cells and Macrophages During the Repair of Peripheral Nerve Injury.Neuroscience bulletin · 2025Review
- Molecular and cellular mechanisms underlying peripheral nerve injury-induced cellular ecological shifts: Implications for neuroregeneration.IBRO neuroscience reports · 2025Review
- Engineering the Immune Response to Biomaterials.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Enhanced mitochondrial function and delivery from adipose-derived stem cell spheres via the EZH2-H3K27me3-PPARγ pathway for advanced therapy.Stem cell research & therapy · 2025Article
- Recombinant Thrombomodulin Domain 1 Modulates Macrophage Polarization and Enhances Healing in Corneal Alkali Burns.Investigative ophthalmology & visual science · 2025Article
- Static Magnetic Stimulation and Magnetic Microwires Synergistically Enhance and Guide Neurite Outgrowth.Advanced healthcare materials · 2025Article
- Engineering Pancreatic Islets to Transiently Codisplay on Their Surface Thrombomodulin and CD47 Immunomodulatory Proteins as a Means of Mitigating Instant Blood-Mediated Inflammatory Reaction following Intraportal Transplantation.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundExcessive inflammation within damaged tissue usually leads to delayed or insufficient regeneration, and nerves in the peripheral nervous system (PNS) generally do not recover fully following damage. Consequently, there is growing interest in whether modulation of the inflammatory response could help to promote nerve regeneration in the PNS. However, to date, there are no practical therapeutic strategies for manipulating inflammation after nerve injury. Thrombomodulin (TM) is a transmembrane glycoprotein containing five domains. The lectin-like domain of TM has the ability to suppress the inflammatory response. However, whether TM can modulate inflammation in the PNS during nerve regeneration has yet to be elucidated.
methodsWe investigated the role of TM in switching proinflammatory type 1 macrophages (M1) to anti-inflammatory type 2 macrophages (M2) in a human monocytic cell line (THP-1) and evaluated the therapeutic application of TM in transected sciatic nerve injury in rats.
resultsThe administration of TM during M1 induction significantly reduced the expression levels of inflammatory cytokines, including TNF-a (p < 0.05), IL-6 (p < 0.05), and CD86 (p < 0.05), in THP-1 cells. Simultaneously, the expression levels of M2 markers, including IL-10 (p < 0.05) and CD206 (p < 0.05), were significantly increased in TM-treated THP-1 cells. Inhibition of IL-4R-c-Myc-pSTAT6-PPARγ signaling abolished the expression levels of IL-10 (p < 0.05) and CD206 (p < 0.05). The conditioned medium (CM) collected from M1 cells triggered an inflammatory response in primary Schwann cells, while CM collected from M1 cells treated with TM resulted in a dose-dependent reduction in inflammation. TM treatment led to better nerve regeneration when tested 6 weeks after injury and preserved effector muscle function. In addition, TM treatment reduced macrophage infiltration at the site of injury and led to potent M1 to M2 transition, thus indicating the anti-inflammatory capacity of TM.
conclusionsCollectively, our findings demonstrate the anti-inflammatory role of TM during nerve regeneration. Therefore, TM represents a potential drug for the promotion and modulation of functional recovery in peripheral nerves that acts by regulating the M1/M2 ratio.
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