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These proteins are essential for tissue formation and cell alignment during the wound healing stage. In particular, FN interacts with collagens to activate various intracellular signaling pathways to maintain ECM stability. A novel recombinant extra domain-B fibronectin (EDB-FN)-COL3A1 fusion protein (rhFEB) was designed to mimic the ECM to promote chronic and refractory skin ulcer wound healing. rhFEB significantly enhanced cell adhesion and migration, vascular ring formation, and the production of new collagen I (COL1A1) in vitro. rhFEB decreased M1 macrophages and further modulated the wound microenvironment, which was confirmed by the treatment of db\/db mice with rhFEB. Accelerated wound healing was shown during the initial stages in rhFEB-treated db\/db mice, as was enhanced follicle regeneration, re-epithelialization, collagen deposition, granulation, inflammation, and angiogenesis. The wound chronicity of diabetic foot ulcers (DFUs) remains the main challenge in current and future treatment. rhFEB may be a candidate molecule for regulating M1 macrophages during DFU healing.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Key points<\/jats:title>\n            <jats:p>\u2022 <jats:italic>A recombinant protein EDB-FN-collagen III (rhFEB)\u00a0was\u00a0highly\u00a0expressed\u00a0in\u00a0Escherichia\u00a0coli<\/jats:italic>\n            <\/jats:p>\n            <jats:p>\u2022 <jats:italic>rhFEB protein induces COL1A1 secretion in human skin fibroblasts<\/jats:italic>\n            <\/jats:p>\n            <jats:p>\u2022 <jats:italic>rhFEB protein accelerates\u00a0diabetic\u00a0wound\u00a0healing<\/jats:italic>\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1007\/s00253-024-13021-9","type":"journal-article","created":{"date-parts":[[2024,1,29]],"date-time":"2024-01-29T11:02:31Z","timestamp":1706526151000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Recombinantly expressed rhFEB remodeled the skin defect of db\/db mice"],"prefix":"10.1007","volume":"108","author":[{"given":"Xiaomin","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinliang","family":"Mao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianhang","family":"Cong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qirong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjie","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kunjun","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yadong","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dun","family":"Su","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9790-5823","authenticated-orcid":false,"given":"Qi","family":"Xiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,1,29]]},"reference":[{"issue":"1","key":"13021_CR1","doi-asserted-by":"publisher","first-page":"5101","DOI":"10.1038\/s41467-019-12987-9","volume":"10","author":"F Barrenas","year":"2019","unstructured":"Barrenas F, Raehtz K, Xu C, Law L, Green RR, Silvestri G, Bosinger SE, Nishida A, Li Q, Lu W, Zhang J, Thomas MJ, Chang J, Smith E, Weiss JM, Dawoud RA, Richter GH, Trichel A, Ma D, Peng X, Komorowski J, Apetrei C, Pandrea I, Gale M Jr (2019) Macrophage-associated wound healing contributes to African green monkey SIV pathogenesis control. 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All experiments were conducted according to the guidelines for animal care and use of China, and they were approved by the animal ethics committee of the Chinese Academy of Medical Sciences.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}],"article-number":"183"}}