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Bone morphogenetic protein 7 (BMP7) confers tissue protective and regenerative functions, but its potential role in diabetic wound healing is unknown. The aim of this study was to investigate the effects of topical BMP7 treatment in wound healing using a streptozotocin-induced diabetic mouse model. The expression of markers of wound healing progression were detected using RT-PCR or immunohistochemistry. Overall, BMP7 improved wound closure, as well as maturation of granulation tissue and collagen deposition, as evidenced by hematoxylin and eosin and Masson\u2019s trichrome histological analysis. The expression of inflammatory markers (IL-6, TNF-\u03b1) and matrix metalloproteinase-9 were decreased in BMP7-treated wounds, together with the number of pro-inflammatory M1 macrophages and T lymphocytes. The number of anti-inflammatory M2 macrophages was increased in BMP7-treated wounds. Moreover, BMP7 decreased oxidative stress and increased Ki67+ cells and CD31+ cells, indicating induced proliferation and angiogenesis in the wound bed compared to the control wounds. Finally, BMP7 activated the ERK pathway and suppressed the p38 pathway in diabetic wounds. Together, our data suggest that BMP7 enhanced skin wound healing in diabetes by decreasing local inflammation and oxidative stress, which promoted a regenerative environment for collagen deposition, wound maturation, cell proliferation, and angiogenesis. These findings underline BMP7 as a potential therapeutic agent for the treatment of skin wounds in diabetes.<\/jats:p>","DOI":"10.3390\/ijms26052036","type":"journal-article","created":{"date-parts":[[2025,2,26]],"date-time":"2025-02-26T06:15:33Z","timestamp":1740550533000},"page":"2036","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Bone Morphogenetic Protein 7 Improves Wound Healing in Diabetes by Decreasing Inflammation and Promoting M2 Macrophage Polarization"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9305-4865","authenticated-orcid":false,"given":"Jessica","family":"Da Silva","sequence":"first","affiliation":[{"name":"Doctoral Program in Experimental Biology and Biomedicine (PDBEB), Institute of Interdisciplinary Research, University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"CNC-UC\u2014Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"CIBB\u2014Centre for Innovative Biomedicine and Biotechnology, University of Coimbra, 3030-788 Coimbra, Portugal"}]},{"given":"Ana","family":"Figueiredo","sequence":"additional","affiliation":[{"name":"CNC-UC\u2014Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"CIBB\u2014Centre for Innovative Biomedicine and Biotechnology, University of Coimbra, 3030-788 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2053-9559","authenticated-orcid":false,"given":"Yu-Hua","family":"Tseng","sequence":"additional","affiliation":[{"name":"Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6264-3632","authenticated-orcid":false,"given":"Eugenia","family":"Carvalho","sequence":"additional","affiliation":[{"name":"CNC-UC\u2014Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"CIBB\u2014Centre for Innovative Biomedicine and Biotechnology, University of Coimbra, 3030-788 Coimbra, Portugal"},{"name":"Institute of Interdisciplinary Research, University of Coimbra, 3004-504 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1748-9861","authenticated-orcid":false,"given":"Ermelindo C.","family":"Leal","sequence":"additional","affiliation":[{"name":"CNC-UC\u2014Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"CIBB\u2014Centre for Innovative Biomedicine and Biotechnology, University of Coimbra, 3030-788 Coimbra, Portugal"},{"name":"Institute of Interdisciplinary Research, University of Coimbra, 3004-504 Coimbra, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,26]]},"reference":[{"key":"ref_1","unstructured":"Magliano, D.J., and Boyko, E.J. 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