Background: A complex interaction between cells and molecules contributes to four phases of wound healing, i.e., hemostasis, inflammation, proliferation, and maturation. Platelet-expressed glycoprotein VI (GPVI) and C-type lectin-like receptor 2 (CLEC-2) function in maintaining vascular integrity to prevent intra-tissue bleeding during skin inflammation. A recent study has shown that lacking both GPVI and CLEC-2 on platelets facilitates wound healing in mice through the impairment of vascular integrity and the associated fibrin/fibrinogen deposition and decreased inflammation. Dasatinib has previously been demonstrated to inhibit Src and Syk, the downstream molecules upon GPVI and CLEC-2 activation, in platelets.

Aims: In this study, we investigated whether dasatinib affects skin wound healing.

Methods: A single full-thickness excisional skin wound (4-mm diameter) was generated on dorsum of 8-week-old C57BL/6 mice. Dasatinib (5 mg/kg or 10 mg/kg) or DMSO (3%) vehicle was intraperitoneally injected immediately after biopsy and then daily for up to 3 days post injury (the inflammatory phase). Wound closure was monitored until day 9 post-injury.

Results: The results showed that dasatinib-treated mice had a significant acceleration in wound closure compared to DMSO-treated mice (n=8). However, there was no difference in wound closure between the two dasatinib-treated groups. During the first 3 days after injury, redness at the wound edge was observed in dasatinib-injected animals but not in controls. In addition, macroscopic observation of inner side of the wound revealed bleeding into the wound of dasatinib-injected mice, suggesting a loss of vascular integrity during this period. Moreover, mice treated with dasatinib had increased fibrinogen content in the wound relative to controls (n=5-6) at day 3 post injury.

Dasatinib enhances skin wound healing by inducing vascular leakage

Conclusions: In conclusion, our results show that dasatinib induces vascular leakage during inflammatory phase of cutaneous wound repair, leading to increased fibrinogen deposition in association with the accelerated rate of wound closure.

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ISTH Congress Abstracts - https://abstracts.isth.org/abstract/dasatinib-impairs-vascular-integrity-and-promotes-skin-wound-healing-in-mice/