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Updated: Jan 11, 2026
Assessment of Acute Wound Healing using the Dorsal Subcutaneous Polyvinyl Alcohol Sponge Implantation and Excisional Tail Skin Wound Models.
Published on: March 25, 2020
MC1R determines healing outcomes in acute and chronic cutaneous wounds
Yonlada Nawilaijaroen1, Holly R Rocliffe1, Shani Austin-Williams2
1Centre for Inflammation Research, Institute for Regeneration and Repair, University of Edinburgh, Edinburgh EH16 4UU, United Kingdom.
Abstract:
Chronic wounds (CWs) represent a major clinical challenge, characterized by persistent inflammation and failed repair. While proresolving pathways are known to regulate inflammatory responses, their potential dysfunction in CWs remains unexplored. Here, we identify dysregulation of the pro-opiomelanocortin-melanocortin 1 receptor (POMC-MC1R) axis as a common feature across pressure ulcers, venous ulcers, and diabetic ulcers. Using MC1Re/e mice lacking functional MC1R, we demonstrate impaired wound healing marked by delayed reepithelialization and increased neutrophil extracellular traps-pathological features observed in human CWs. To investigate MC1R's therapeutic potential, we developed a new murine CW model that replicates human pathology, presenting as nonhealing, exudate-rich ulcers. Topical application of the MC1R-selective agonist BMS-470539 restored healing by reducing exudate production, stimulating vascularization, and enabling reepithelialization. The critical role of MC1R was further evidenced by MC1Re/e mice, which developed more severe ulcers with excessive exudate and NETosis. In acute wound studies, we found that topical MC1R agonist enhanced wound bed perfusion and lymphatic drainage through increased angiogenesis and lymphangiogenesis and reduced scarring by modulating fibroblast phenotype. Together, these findings establish the MC1R/POMC axis as a fundamental regulator of skin repair and identify promising therapeutic strategies to drive healing.
Insights
Dysfunctional pro-opiomelanocortin-melanocortin 1 receptor (POMC-MC1R) signaling impairs chronic wound healing. Targeting MC1R with agonists promotes repair by reducing inflammation and enhancing tissue regeneration.
Area of Science:
- Dermatology
- Wound Healing Research
- Molecular Medicine
Background:
- Chronic wounds (CWs) exhibit persistent inflammation and failed repair, with proresolving pathway dysfunction largely unexplored.
- The pro-opiomelanocortin-melanocortin 1 receptor (POMC-MC1R) axis is implicated in inflammatory responses but its role in CWs is unknown.
Purpose of the Study:
- To investigate the role of the POMC-MC1R axis in chronic wound pathophysiology.
- To evaluate the therapeutic potential of MC1R agonists in promoting chronic wound healing.
Main Methods:
- Utilized MC1Re/e mice lacking functional MC1R to model impaired wound healing.
- Developed a novel murine chronic wound model mimicking human pathology.
- Administered a selective MC1R agonist (BMS-470539) topically in wound models.
- Assessed wound healing parameters including reepithelialization, exudate, vascularization, and neutrophil extracellular traps (NETosis).
Main Results:
- MC1R deficiency in mice resulted in delayed reepithelialization and increased NETosis, mirroring human CW features.
- Topical MC1R agonist treatment in a murine CW model restored healing by reducing exudate, enhancing vascularization, and promoting reepithelialization.
- MC1R agonists improved wound bed perfusion and lymphatic drainage via angiogenesis and lymphangiogenesis, while reducing scarring.
- MC1Re/e mice exhibited exacerbated ulcer severity, increased exudate, and heightened NETosis.
Conclusions:
- The POMC-MC1R axis is a critical regulator of skin repair processes.
- Dysregulation of MC1R contributes to the pathology of chronic wounds.
- MC1R agonists represent a promising therapeutic strategy for accelerating chronic wound healing.
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