Vascular endothelial Cdc42 deficiency delays skin wound-healing processes by increasing IL-1β and TNF-α expression.

Angiogenesis is an important step in skin wound repair. Angiogenesis is affected by the functions of many types of cells, especially endothelial cells. Cdc42 plays a vital role in endothelial cell function and vascular development; however, the role of Cdc42 in skin microvascular permeability and skin wound healing is unclear. This study investigated the involvement of Cdc42 in skin wound-healing processes based on its known roles in angiogenesis. Full-thickness skin wounds were created on wild-type and inducible vascular-endothelial-specific Cdc42-/- mice. Cdc42 deletion in endothelium affected wound healing in following ways. Reepithelialization of wounds in Cdc42-/- mice was delayed compared with that of wounds in wild-type mice. The degree of angiogenesis of wound granulation tissue was significantly lower in Cdc42-/- mice than in wild-type mice. Infiltration of F4/80+ macrophages and the expression of MCP-1, IL-1β, and TNF-α were increased in the wound bed of Cdc42-/- mice compared with wild-type mice. These results confirm that Cdc42 in endothelium is required for angiogenesis and is an essential regulator of key skin wound-healing processes.