GPCRs as key regulators in wound healing
Summary: This 2026 review explores the critical role of G-protein-coupled receptors (GPCRs) in orchestrating wound healing phases (hemostasis, inflammation, proliferation, remodeling). GPCRs modulate immune cell chemotaxis, platelet aggregation, keratinocyte migration/proliferation, macrophage polarization, and key signaling cascades including Hedgehog-GLI, Hippo-YAP/TAZ, and Wnt/β-catenin. In diabetic and chronic wounds, specific GPCRs (e.g., P2Y12, CXCR4, BLT2, AT1R) influence inflammation resolution, angiogenesis, and re-epithelialization. Agonists/antagonists targeting GPCRs show promise for accelerating healing, with examples including prostacyclin analogs for DFU perfusion and CXCR4 antagonists for progenitor cell recruitment. The review highlights GPCRs as versatile drug targets for improving outcomes in hard-to-heal wounds.
Key Highlights:
- GPCRs regulate immune infiltration, cell migration, and multiple healing pathways (Hedgehog, Hippo, Wnt)
- Relevance to DFU: P2Y12 promotes resolution; CXCR4 antagonism and BLT2 activation improve diabetic healing
- Therapeutic examples: beraprost/iloprost, losartan, AMD3100, PGE2 hydrogels
- Authors: Haidi Chen, Kun Zheng, Yue Xiao, Xun Feng, Chang Zhang, Ting Zhang
Read full article (open access)
Keywords: GPCRs wound healing, chronic wound mechanisms, diabetic foot ulcer therapy, macrophage polarization, Haidi Chen