CLEC14A facilitates angiogenesis and alleviates inflammation in diabetic wound healing

Background: Delayed wound healing is a serious complication of diabetic wounds, posing a significant challenge to the treatment of patients with diabetes. Diabetic wound healing is a complex dynamic process involving angiogenesis and inflammatory responses. Currently, there are limited targeted therapies to promote diabetic wound healing. This study aimed to reveal the role of CLEC14A in the process of diabetic wound healing, with the hope of identifying new therapeutic targets to accelerate the healing of diabetic wounds. Methods: In vivo, diabetic mice were generated by combined streptozotocin (STZ) and high-fat diet treatment. The wound healing model was established in wild-type and Clec14a- /- diabetic mice. The degree of wound healing, as well as angiogenesis and inflammation during the healing process, were evaluated through Hematoxylin and Eosin (H&E) staining, immunohistochemical staining, and immunofluorescence staining. In vitro, the angiogenic activities of Human Umbilical Vein Endothelial Cells (HUVECs) were assessed following treatment with high glucose and adenoviruses overexpressing CLEC14A, using scratch assays and tube formation assays. Interleukin1 beta (IL-1 beta) and Tumor Necrosis Factor-alpha (TNF-alpha) were utilized to evaluate the levels of inflammation in HUVECs. Results: CLEC14A expression was suppressed in diabetic wounds. Deletion of the Clec14a inhibited angiogenesis and activated inflammatory responses in vivo. High-glucose treatment led to decreased CLEC14A expression, impaired angiogenic capacity, and elevated inflammatory levels in vitro. However, adenoviral-mediated overexpression of CLEC14A reversed the response induced by high glucose. Conclusion: CLEC14A accelerates diabetic wound healing by promoting angiogenesis and reducing wound inflammation.