The Crosstalk Between Efferocytosis and Macrophage Polarization in Diabetic Wounds: A Comprehensive Review
Summary: This comprehensive 2026 review examines how defective efferocytosis (clearance of apoptotic cells) in the diabetic wound microenvironment impairs the transition of macrophages from pro-inflammatory M1 to pro-healing M2 phenotype, leading to persistent inflammation and delayed healing. Hyperglycemia, AGEs, oxidative stress, hypoxia, biofilms, and senescence disrupt efferocytosis receptors (e.g., MerTK) and signaling pathways including JAK/STAT, PI3K/Akt, NLRP3 inflammasome, NF-κB, and MAPK. Failed efferocytosis deprives macrophages of anti-inflammatory signals (TGF-β, IL-10), locking them in M1 dominance. The review discusses therapeutic strategies such as small molecules, natural compounds, and biomaterials (e.g., MerTK nanoparticles, hydrogels) to restore efferocytosis and promote M2 polarization, offering new avenues to overcome limitations in current diabetic wound treatments.
Key Highlights:
- Impaired efferocytosis blocks M1-to-M2 switch in diabetic wounds
- Key disrupted pathways: MerTK downregulation, NLRP3 activation, NF-κB sustained signaling
- Potential therapies target AC clearance and polarization reprogramming
- Authors: Yuxin He, Jie Hu, Anqi Ma, Peiyang Du, Mengdie Yang
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Keywords: efferocytosis, macrophage polarization diabetic, diabetic wound inflammation, Yuxin He