College of Stomatology, Chongqing Medical University, Chongqing 401147, China; Chongqing Key Laboratory of Oral Diseases, Chongqing 401147, China.
College of Stomatology, Chongqing Medical University, Chongqing 401147, China; Chongqing Key Laboratory of Oral Diseases, Chongqing 401147, China.
Life Sci. 2024 Dec 1;358:123176. doi: 10.1016/j.lfs.2024.123176. Epub 2024 Oct 24.
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.
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. Interleukin-1β (IL-1β) and Tumor Necrosis Factor-α (TNF-α) were utilized to evaluate the levels of inflammation in HUVECs.
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.
CLEC14A accelerates diabetic wound healing by promoting angiogenesis and reducing wound inflammation.
糖尿病患者的伤口愈合延迟是一种严重的并发症，对糖尿病患者的治疗构成了重大挑战。糖尿病伤口愈合是一个涉及血管生成和炎症反应的复杂动态过程。目前，促进糖尿病伤口愈合的靶向治疗方法有限。本研究旨在揭示 CLEC14A 在糖尿病伤口愈合过程中的作用，以期发现新的治疗靶点，加速糖尿病伤口的愈合。
体内实验中，通过联合链脲佐菌素（STZ）和高脂饮食处理构建糖尿病小鼠模型。在野生型和 Clec14a 糖尿病小鼠中建立伤口愈合模型。通过苏木精和伊红（H&E）染色、免疫组织化学染色和免疫荧光染色评估伤口愈合程度以及愈合过程中的血管生成和炎症反应。体外实验中，通过划痕实验和管形成实验评估高糖和过表达 CLEC14A 的腺病毒处理后对人脐静脉内皮细胞（HUVEC）的血管生成活性。采用白细胞介素-1β（IL-1β）和肿瘤坏死因子-α（TNF-α）评估 HUVEC 中的炎症水平。
CLEC14A 在糖尿病伤口中表达受抑制。Clecl4a 缺失抑制体内血管生成并激活炎症反应。高糖处理导致 CLEC14A 表达降低，体外血管生成能力受损，炎症水平升高。然而，腺病毒介导的 CLEC14A 过表达逆转了高糖诱导的反应。
CLEC14A 通过促进血管生成和减少伤口炎症加速糖尿病伤口愈合。
