Akhirin Preserves Hemostatic Wound Repair Through Non-Hematopoietic Regulation of the Vascular Injury Microenvironment.

Hemostasis and wound healing are highly coordinated processes that involve rapid clot formation followed by controlled remodeling of the injured tissue microenvironment. Prior work on Akhirin (AKH), a secreted extracellular matrix protein containing two von Willebrand factor A domains and an LCCL domain, has established it as a regulator of the neural stem niche in the developing brain and spinal cord injury microenvironment. However, its role as a non-hematopoietic molecule in the vascular injury response remains unknown. Here, we present evidence that AKH contributes to hemostasis and wound repair outside the neural niche. Our immunohistochemical and biochemical analyses demonstrated AKH around arterial tissues, suggesting a potential role at the blood-vessel interface. AKH-deficient mice exhibited a striking phenotype characterized by prolonged tail bleeding and delayed wound closure, indicating impaired vascular injury repair in vivo. Furthermore, bone marrow transplantation failed to rescue the prolonged bleeding phenotype, supporting a predominant non-hematopoietic contribution. Intriguingly, analysis of classical coagulation revealed an apparent paradox: activated partial thromboplastin time was shortened, whereas prothrombin time was not significantly altered. In contrast, increased expression of tissue plasminogen activator, urokinase-type plasminogen activator, and urokinase-type plasminogen activator receptor in AKH-deficient samples suggested dysregulated local fibrinolytic remodeling. Together, these findings identify AKH as a previously unrecognized extracellular regulator of hemostatic wound repair. Rather than indicating a defect in classical coagulation cascade activation, the findings associate AKH deficiency with impaired hemostatic control and altered expression of plasminogen activator system components, suggesting a role for AKH in the local vascular injury response.