Exosomal coactivator-associated arginine methyltransferase 1 derived from adipocytes accelerates diabetic wound healing by modulating inflammation and promoting angiogenesis
IntroductionDelayed wound healing remains a significant clinical challenge under diabetic conditions, characterized by chronic inflammation and impaired angiogenesis. Traditional treatments show limited efficacy, highlighting the urgent need for innovative therapeutic approaches.MethodsThis study in...
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Frontiers Media S.A.
2025-08-01
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| Series: | Frontiers in Bioengineering and Biotechnology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fbioe.2025.1610806/full |
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| author | Yongxiang Zhang Yao Pan Kai Yang Xiansun Wu Yaoyao Zhang Fengbiao Xu Tietao Di Tietao Di Wang Liu |
| author_facet | Yongxiang Zhang Yao Pan Kai Yang Xiansun Wu Yaoyao Zhang Fengbiao Xu Tietao Di Tietao Di Wang Liu |
| author_sort | Yongxiang Zhang |
| collection | DOAJ |
| description | IntroductionDelayed wound healing remains a significant clinical challenge under diabetic conditions, characterized by chronic inflammation and impaired angiogenesis. Traditional treatments show limited efficacy, highlighting the urgent need for innovative therapeutic approaches.MethodsThis study investigated the therapeutic potential of exosomes derived from subcutaneous adipocytes (Adipo-EVs) using a diabetic mouse model. Adipo-EVs were locally administered to full-thickness wounds, and healing efficiency was evaluated through wound closure kinetics, histopathology (H&E, Masson’s trichrome), immunohistochemistry (Ki67,α-SMA), and molecular analysis (qPCR, proteomics). The role of the enriched protein Carm1 was validated via siRNA knockdown in vitro and in vivo.ResultsAdipo-EVs significantly accelerated wound closure, increased cellular proliferation, enhanced collagen deposition, and improved myofibroblast differentiation. Mechanistically, Adipo-EVs suppressed pro-inflammatory cytokines (IL-6, TNF-α) while upregulating IL-10 and promoting angiogenesis (elevated CD31+ vessels and in vitro tube formation). Proteomic analysis identified Carm1 as a highly enriched mediator in Adipo-EVs. Knockdown of Carm1 abolished the anti-inflammatory and angiogenic effects of Adipo-EVs, leading to impaired wound repair.DiscussionOur findings demonstrate that exosomal Carm1 critically modulates inflammation and angiogenesis to enhance diabetic wound healing. This study reveals Carm1 as a pivotal therapeutic component of adipocyte-derived exosomes, offering a novel strategy for managing chronic diabetic wounds. |
| format | Article |
| id | doaj-art-72a425e53fa44cfda55b33641d98f21e |
| institution | Kabale University |
| issn | 2296-4185 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Bioengineering and Biotechnology |
| spelling | doaj-art-72a425e53fa44cfda55b33641d98f21e2025-08-21T05:27:17ZengFrontiers Media S.A.Frontiers in Bioengineering and Biotechnology2296-41852025-08-011310.3389/fbioe.2025.16108061610806Exosomal coactivator-associated arginine methyltransferase 1 derived from adipocytes accelerates diabetic wound healing by modulating inflammation and promoting angiogenesisYongxiang Zhang0Yao Pan1Kai Yang2Xiansun Wu3Yaoyao Zhang4Fengbiao Xu5Tietao Di6Tietao Di7Wang Liu8Department of Orthopedics, The 2nd Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guizhou University of Traditional Chinese Medicine, Guiyang, ChinaGraduate School, Guizhou University of Traditional Chinese Medicine, Guiyang, ChinaDepartment of Orthopedics, Ningxiang Hospital of Traditional Chinese Medicine, Ningxiang, ChinaDepartment of Orthopedics, Ningxiang Hospital of Traditional Chinese Medicine, Ningxiang, ChinaDepartment of Orthopedics, The 2nd Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guizhou University of Traditional Chinese Medicine, Guiyang, ChinaDepartment of Orthopedics, Ningxiang Hospital of Traditional Chinese Medicine, Ningxiang, ChinaDepartment of Orthopedics, The 2nd Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guizhou University of Traditional Chinese Medicine, Guiyang, ChinaGraduate School, Guizhou University of Traditional Chinese Medicine, Guiyang, ChinaDepartment of Orthopedics, Ningxiang Hospital of Traditional Chinese Medicine, Ningxiang, ChinaIntroductionDelayed wound healing remains a significant clinical challenge under diabetic conditions, characterized by chronic inflammation and impaired angiogenesis. Traditional treatments show limited efficacy, highlighting the urgent need for innovative therapeutic approaches.MethodsThis study investigated the therapeutic potential of exosomes derived from subcutaneous adipocytes (Adipo-EVs) using a diabetic mouse model. Adipo-EVs were locally administered to full-thickness wounds, and healing efficiency was evaluated through wound closure kinetics, histopathology (H&E, Masson’s trichrome), immunohistochemistry (Ki67,α-SMA), and molecular analysis (qPCR, proteomics). The role of the enriched protein Carm1 was validated via siRNA knockdown in vitro and in vivo.ResultsAdipo-EVs significantly accelerated wound closure, increased cellular proliferation, enhanced collagen deposition, and improved myofibroblast differentiation. Mechanistically, Adipo-EVs suppressed pro-inflammatory cytokines (IL-6, TNF-α) while upregulating IL-10 and promoting angiogenesis (elevated CD31+ vessels and in vitro tube formation). Proteomic analysis identified Carm1 as a highly enriched mediator in Adipo-EVs. Knockdown of Carm1 abolished the anti-inflammatory and angiogenic effects of Adipo-EVs, leading to impaired wound repair.DiscussionOur findings demonstrate that exosomal Carm1 critically modulates inflammation and angiogenesis to enhance diabetic wound healing. This study reveals Carm1 as a pivotal therapeutic component of adipocyte-derived exosomes, offering a novel strategy for managing chronic diabetic wounds.https://www.frontiersin.org/articles/10.3389/fbioe.2025.1610806/fulladipocyte-derived exosomesdiabetic wound healingangiogenesisinflammationCarm1 |
| spellingShingle | Yongxiang Zhang Yao Pan Kai Yang Xiansun Wu Yaoyao Zhang Fengbiao Xu Tietao Di Tietao Di Wang Liu Exosomal coactivator-associated arginine methyltransferase 1 derived from adipocytes accelerates diabetic wound healing by modulating inflammation and promoting angiogenesis Frontiers in Bioengineering and Biotechnology adipocyte-derived exosomes diabetic wound healing angiogenesis inflammation Carm1 |
| title | Exosomal coactivator-associated arginine methyltransferase 1 derived from adipocytes accelerates diabetic wound healing by modulating inflammation and promoting angiogenesis |
| title_full | Exosomal coactivator-associated arginine methyltransferase 1 derived from adipocytes accelerates diabetic wound healing by modulating inflammation and promoting angiogenesis |
| title_fullStr | Exosomal coactivator-associated arginine methyltransferase 1 derived from adipocytes accelerates diabetic wound healing by modulating inflammation and promoting angiogenesis |
| title_full_unstemmed | Exosomal coactivator-associated arginine methyltransferase 1 derived from adipocytes accelerates diabetic wound healing by modulating inflammation and promoting angiogenesis |
| title_short | Exosomal coactivator-associated arginine methyltransferase 1 derived from adipocytes accelerates diabetic wound healing by modulating inflammation and promoting angiogenesis |
| title_sort | exosomal coactivator associated arginine methyltransferase 1 derived from adipocytes accelerates diabetic wound healing by modulating inflammation and promoting angiogenesis |
| topic | adipocyte-derived exosomes diabetic wound healing angiogenesis inflammation Carm1 |
| url | https://www.frontiersin.org/articles/10.3389/fbioe.2025.1610806/full |
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