PB0864 - Platelet secretion in wound healing: the essence of α-granule endocytosis, biogenesis, and release kinetics

Background: Wound healing is a multi-step process involving different cell types and growth factors. Though platelet-rich plasma has been used to accelerate wound repair, functional understanding of how platelet functions affect wound healing is limited.

Aims: Investigate the role of platelet secretion in a full-thickness wound model.

Methods: Dorsal full-thickness excisions were made on mice defective in platelet α-granule biogenesis, exocytosis, endocytosis, and C57BL/6J control mice. Wounds were measured daily to assess healing progression. On days 3 and 7, wound sites were harvested for histology. Bioactive molecules were analysed from extracts prepared from the wound tissue.

Results: Nbeal2-/- mice have defective platelet granule biogenesis and cargo packaging, and showed severely impaired wound healing with distinctive wound morphology. The platelet-specific Arf6-/- and VAMP2/3∆ mice, which have improper endocytic trafficking and fibrinogen uptake/storage, also showed remarkably slower wound healing. Interestingly, Munc13-4Jinx mice, having no dense and delayed α-granule release, presented with substantially faster healing, specifically in the first days after wounding. In histological wound sections, Munc13-4Jinx and Serglycin-/- mice resembled wound healing and morphology of C57BL/6J mice. Delayed wound healing progression in Nbeal2-/- mice was reflected by decreased wound keratin content three days after wounding. Over the course of wound healing, levels of various bioactive molecules changed. Most of the ones examined decreased during wound resolution, except for FGF2 and MMP-9, reflecting wound remodelling. These trends were altered in Nbeal2-/- mice, where FGF2 and MMP-9 levels decreased as the wounds healed. The correlation slope between wound resolution and IL-1β, MMP-3, TIMP-1, and VEGF levels was less steep or even flat in Nbeal2-/- mice compared to the other strains.

Conclusion(s): Our data show that platelet functions have specific roles in wound healing progression and may impact the presence and levels of various bioactive molecules in the wounded tissue.

Supported by the AHA (1020159), NIH/NHLBI (HL150818), and the VA.