{"title":"血管内皮生长因子通过促进 M2 巨噬细胞极化加速糖尿病大鼠足部溃疡的愈合。","authors":"Fei Liu, Xianrui Xu, Tao Sun","doi":"10.1111/dme.15388","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Aim</h3>\n \n <p>The objective was to investigate the specific role and the regulatory mechanism of vascular endothelial growth factor (VEGF) during wound healing in diabetic foot ulcer (DFU).</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>Streptozotocin-induced diabetic rats were used to establish a DFU animal model. VEGF and Axitinib (a specific inhibitor of VEGFR) were used for treatment in vivo. The wounds at different time points were imaged and histological analysis of the wounds were performed by haematoxylin and eosin (H&E) staining and Masson's trichrome staining. Immunohistochemical staining was conducted to examine CD31 and eNOS expression in the wounds. Immunofluorescence assay and quantitative real-time PCR were performed to examine macrophage markers. In addition, THP-1 was differentiated to macrophages, and then treated with interleukin (IL)-4 to induce M2 macrophages, followed by VEGF treatment. The conditional medium (CM) from VEGF-mediated macrophages were collected to culture human dermal fibroblasts (HDFs). Cell viability and migration were measured by Cell Counting Kit (CCK)-8, wound-healing and Transwell assays, respectively.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>VEGF treatment remarkably accelerated wound healing of DFU rats. VEGF promoted collagen deposition and elevated CD31 and eNOS expression, confirming the pro-angiogenesis of VEGF around diabetic wound in rats. Meanwhile, VEGF restricted pro-inflammatory cytokines and increased F4/80 and CD206 expression, highlighting the activated macrophages and enhanced M2 macrophages following VEGF treatment in diabetic wounds of DFU rats. However, Axitinib exerted an opposite function to VEGF in DFU rats. Moreover, VEGF directly promoted macrophage polarization toward M2 phenotype in vitro, and the CM from VEGF-mediated M2 macrophages markedly promoted HDFs proliferation, migration and collagen deposition.</p>\n </section>\n \n <section>\n \n <h3> Conclusion</h3>\n \n <p>VEGF might accelerate the wound healing of DFU through promoting M2 macrophage polarization and fibroblast migration.</p>\n </section>\n </div>","PeriodicalId":11251,"journal":{"name":"Diabetic Medicine","volume":null,"pages":null},"PeriodicalIF":3.2000,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Vascular endothelial growth factor accelerates healing of foot ulcers in diabetic rats via promoting M2 macrophage polarization\",\"authors\":\"Fei Liu, Xianrui Xu, Tao Sun\",\"doi\":\"10.1111/dme.15388\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Aim</h3>\\n \\n <p>The objective was to investigate the specific role and the regulatory mechanism of vascular endothelial growth factor (VEGF) during wound healing in diabetic foot ulcer (DFU).</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>Streptozotocin-induced diabetic rats were used to establish a DFU animal model. VEGF and Axitinib (a specific inhibitor of VEGFR) were used for treatment in vivo. The wounds at different time points were imaged and histological analysis of the wounds were performed by haematoxylin and eosin (H&E) staining and Masson's trichrome staining. Immunohistochemical staining was conducted to examine CD31 and eNOS expression in the wounds. Immunofluorescence assay and quantitative real-time PCR were performed to examine macrophage markers. In addition, THP-1 was differentiated to macrophages, and then treated with interleukin (IL)-4 to induce M2 macrophages, followed by VEGF treatment. The conditional medium (CM) from VEGF-mediated macrophages were collected to culture human dermal fibroblasts (HDFs). Cell viability and migration were measured by Cell Counting Kit (CCK)-8, wound-healing and Transwell assays, respectively.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>VEGF treatment remarkably accelerated wound healing of DFU rats. VEGF promoted collagen deposition and elevated CD31 and eNOS expression, confirming the pro-angiogenesis of VEGF around diabetic wound in rats. Meanwhile, VEGF restricted pro-inflammatory cytokines and increased F4/80 and CD206 expression, highlighting the activated macrophages and enhanced M2 macrophages following VEGF treatment in diabetic wounds of DFU rats. However, Axitinib exerted an opposite function to VEGF in DFU rats. Moreover, VEGF directly promoted macrophage polarization toward M2 phenotype in vitro, and the CM from VEGF-mediated M2 macrophages markedly promoted HDFs proliferation, migration and collagen deposition.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Conclusion</h3>\\n \\n <p>VEGF might accelerate the wound healing of DFU through promoting M2 macrophage polarization and fibroblast migration.</p>\\n </section>\\n </div>\",\"PeriodicalId\":11251,\"journal\":{\"name\":\"Diabetic Medicine\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.2000,\"publicationDate\":\"2024-06-27\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Diabetic Medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1111/dme.15388\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"ENDOCRINOLOGY & METABOLISM\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Diabetic Medicine","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/dme.15388","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
Vascular endothelial growth factor accelerates healing of foot ulcers in diabetic rats via promoting M2 macrophage polarization
Aim
The objective was to investigate the specific role and the regulatory mechanism of vascular endothelial growth factor (VEGF) during wound healing in diabetic foot ulcer (DFU).
Methods
Streptozotocin-induced diabetic rats were used to establish a DFU animal model. VEGF and Axitinib (a specific inhibitor of VEGFR) were used for treatment in vivo. The wounds at different time points were imaged and histological analysis of the wounds were performed by haematoxylin and eosin (H&E) staining and Masson's trichrome staining. Immunohistochemical staining was conducted to examine CD31 and eNOS expression in the wounds. Immunofluorescence assay and quantitative real-time PCR were performed to examine macrophage markers. In addition, THP-1 was differentiated to macrophages, and then treated with interleukin (IL)-4 to induce M2 macrophages, followed by VEGF treatment. The conditional medium (CM) from VEGF-mediated macrophages were collected to culture human dermal fibroblasts (HDFs). Cell viability and migration were measured by Cell Counting Kit (CCK)-8, wound-healing and Transwell assays, respectively.
Results
VEGF treatment remarkably accelerated wound healing of DFU rats. VEGF promoted collagen deposition and elevated CD31 and eNOS expression, confirming the pro-angiogenesis of VEGF around diabetic wound in rats. Meanwhile, VEGF restricted pro-inflammatory cytokines and increased F4/80 and CD206 expression, highlighting the activated macrophages and enhanced M2 macrophages following VEGF treatment in diabetic wounds of DFU rats. However, Axitinib exerted an opposite function to VEGF in DFU rats. Moreover, VEGF directly promoted macrophage polarization toward M2 phenotype in vitro, and the CM from VEGF-mediated M2 macrophages markedly promoted HDFs proliferation, migration and collagen deposition.
Conclusion
VEGF might accelerate the wound healing of DFU through promoting M2 macrophage polarization and fibroblast migration.
期刊介绍：
Diabetic Medicine, the official journal of Diabetes UK, is published monthly simultaneously, in print and online editions.
The journal publishes a range of key information on all clinical aspects of diabetes mellitus, ranging from human genetic studies through clinical physiology and trials to diabetes epidemiology. We do not publish original animal or cell culture studies unless they are part of a study of clinical diabetes involving humans. Categories of publication include research articles, reviews, editorials, commentaries, and correspondence. All material is peer-reviewed.
We aim to disseminate knowledge about diabetes research with the goal of improving the management of people with diabetes. The journal therefore seeks to provide a forum for the exchange of ideas between clinicians and researchers worldwide. Topics covered are of importance to all healthcare professionals working with people with diabetes, whether in primary care or specialist services.
Surplus generated from the sale of Diabetic Medicine is used by Diabetes UK to know diabetes better and fight diabetes more effectively on behalf of all people affected by and at risk of diabetes as well as their families and carers.”
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