CD93 Ameliorates Diabetic Wounds by Promoting Angiogenesis via the p38MAPK/MK2/HSP27 Axis

作者全名："Xu, Yuan; Jia, Yuhuan; Wu, Na; Wang, Jie; He, Liwen; Yang, Deqin"

作者地址："[Xu, Yuan; Jia, Yuhuan; Wu, Na; Wang, Jie; He, Liwen; Yang, Deqin] Chongqing Med Univ, Coll Stomatol, Chongqing, Peoples R China; [Xu, Yuan; Jia, Yuhuan; Wu, Na; Wang, Jie; He, Liwen; Yang, Deqin] Chongqing Key Lab Oral Dis & Biomed Sci, Chongqing, Peoples R China; [Xu, Yuan; Jia, Yuhuan; Wu, Na; Wang, Jie; He, Liwen; Yang, Deqin] Chongqing Municipal Key Lab Oral Biomed Engn Highe, Chongqing, Peoples R China; [Yang, Deqin] Chongqing Key Lab Oral Dis & Biomed Sci, 426 Songshi North Rd, Chongqing 401147, Peoples R China"

通信作者："Yang, DQ (通讯作者)，Chongqing Key Lab Oral Dis & Biomed Sci, 426 Songshi North Rd, Chongqing 401147, Peoples R China."

来源：EUROPEAN JOURNAL OF VASCULAR AND ENDOVASCULAR SURGERY

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:001112332400001

JCR分区：Q1

影响因子：5.7

年份：2023

卷号：66

期号：5

开始页：707

结束页：721

文献类型：Article

关键词：Angiogenesis; CD93; Diabetic wound; p38MAPK; Re-epithelisation

摘要："Objective: Diabetic wounds are a complication of diabetes mellitus, which is characterised by microcirculation dysfunction caused by decreased local blood supply and insufficient metabolic exchange. Clinically, in addition to glycaemic control, the most important treatment for diabetic wounds is to promote local angiogenesis, which accelerates wound healing. The authors previous study demonstrated that CD93, which is specifically expressed on vascular endothelial cells (ECs), redundantly regulates angiogenesis in zebrafish, suggesting that CD93 is a potential angiogenic molecule. However, the role of CD93 in diabetic wounds has not yet been elucidated. Methods: The angiogenic effects of CD93 were studied from four aspects: exogenous, endogenous, in vitro, and in vivo. CD93 recombinant protein was used in microvascular ECs and in mice to observe angiogenesis in vitro and in vivo. The wound model was established in CD93-/- and wild type diabetic mice, and the degree of wound healing as well as the amount and maturity of neovascularisation were investigated. The possible mechanism of CD93 in angiogenesis was determined by CD93 overexpression in cultured ECs. Results: CD93 recombinant protein was found to exogenously promote tube formation and sprouting of ECs. It also recruited cells to promote the formation of vascular like structures in subcutaneous tissue and accelerated wound healing by optimising angiogenesis and re-epithelisation. Furthermore, CD93 deficiency was observed to delay wound repair, characterised by reduced neovascularisation, vascular maturity, and re-epithelisation level. Mechanically, CD93 activated the p38MAPK/MK2/HSP27 signalling pathway, positively affecting the angiogenic functions of ECs. Conclusion: This study demonstrated that CD93 promotes angiogenesis both in vitro and in vivo and that its angiogenic role in vitro is mediated by the p38MAPK/MK2/HSP27 signalling pathway. It was also found that CD93 exerts beneficial effects on wound healing in diabetic mice by promoting angiogenesis and re-epithelisation."

基金机构："National Natural Science Foundation of China [31970783, 32270888]; Program for Top Talent Distinguished Professor from Chongqing Medical University [[2021] 215]; Program for Youth Innovation in Future Medicine from Chongqing Medical University [W0060]"

基金资助正文："The reported work was supported in part by research grants from projects supported by the National Natural Science Foundation of China [No. 31970783 and No. 32270888 to D.Y.], Program for Top Talent Distinguished Professor from Chongqing Medical University [No. [2021] 215 to D.Y.], and Program for Youth Innovation in Future Medicine from Chongqing Medical University [No. W0060 to D.Y.]."