Botulinum toxin A prevents hypertrophic scarring by suppressing PARP14/SOCS2-mediated M2 polarization of macrophages.

Summary

In a hypertrophic scar mouse model, botulinum toxin A reduced dermal thickness, epidermal hyperplasia, collagen deposition, fibrosis, proliferation, angiogenesis, and M2 macrophage markers. Mechanistically, BTX-A suppressed PARP14 and SOCS2 expression; PARP14 stabilized SOCS2 mRNA, and PARP14 overexpression rescued M2 polarization and scar features, while SOCS2 silencing counteracted these effects.

Key Findings

• BTX-A dose-dependently reduced dermal thickness, epidermal hyperplasia, and collagen deposition in a hypertrophic scar mouse model.
• BTX-A decreased fibrosis, proliferation, angiogenesis, and M2 macrophage markers in vivo and in a THP-1-derived M2 macrophage–human dermal fibroblast co-culture.
• RNA-seq and functional assays identified PARP14/SOCS2 as a pathway suppressed by BTX-A; PARP14 stabilized SOCS2 mRNA, and PARP14 overexpression reversed BTX-A effects.

Clinical Implications

Supports clinical exploration of perioperative/early BTX-A to prevent hypertrophic scars and prioritizes PARP14/SOCS2 as biomarkers or targets for antifibrotic strategies.

Limitations

• Preclinical model; human translatability and optimal dosing/timing remain to be defined
• Long-term scar remodeling outcomes and safety endpoints were not assessed

Future Directions

Pilot clinical trials testing perioperative BTX-A for scar prevention, and development of PARP14/SOCS2-directed antifibrotic interventions or biomarkers.