Exosomal miRNA-155-5p from M1-polarized macrophages suppresses angiogenesis by targeting GDF6 to interrupt diabetic wound healing
Unprogrammed macrophage polarization, especially prolonged activation of proinflammatory macrophages, is associated with delayed wound healing in diabetic objectives. Macrophage-derived exosomes cargo a variety of microRNAs (miRNAs), participating in different stages in wound healing. Here, exosomes...
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| Format: | Article |
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Elsevier
2023-12-01
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| Series: | Molecular Therapy: Nucleic Acids |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2162253123002925 |
| _version_ | 1827687035871166464 |
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| author | Ruohan Lou Jiali Chen Fei Zhou Tian Zhang Xiuping Chen Chunming Wang Bing Guo Ligen Lin |
| author_facet | Ruohan Lou Jiali Chen Fei Zhou Tian Zhang Xiuping Chen Chunming Wang Bing Guo Ligen Lin |
| author_sort | Ruohan Lou |
| collection | DOAJ |
| description | Unprogrammed macrophage polarization, especially prolonged activation of proinflammatory macrophages, is associated with delayed wound healing in diabetic objectives. Macrophage-derived exosomes cargo a variety of microRNAs (miRNAs), participating in different stages in wound healing. Here, exosomes were isolated from naive bone marrow–derived macrophages (BMDMs) (M0-Exos), interferon-γ plus lipopolysaccharide-polarized BMDMs (M1-Exos), and interleukin-4-polarized BMDMs (M2-Exos). M1-Exos impaired migration and tube formation in human umbilical vein endothelial cells (HUVECs) compared to M0-Exos, whereas M2-Exos exhibited the opposite effects. High-throughput sequencing was performed to decipher the miRNA expression profiles in M0-Exos, M1-Exos, and M2-Exos. A total of 63 miRNAs were identified to be differentially expressed in exosomes derived from polarized BMDMs. Among them, miRNA-155-5p is highly expressed in M1-Exos, which interrupted angiogenesis in HUVECs. Furthermore, miRNA-155-5p directly binds to the 3′ UTR of growth differentiation factor 6 (GDF6) mRNA to suppress its protein expression. Lastly, local administration of a temperature-sensitive hydrogel Pluronic F-127 loading miRNA-155-5p antagomiR promoted angiogenesis and accelerated wound healing in diabetic db/db mice via enhancing GDF6. In summary, this study deciphered the miRNA expression profiles in exosomes from polarized macrophages. M2-like macrophage-derived exosomes and miRNA-155-5p inhibitors could be promising therapeutics against diabetic foot ulcers. |
| first_indexed | 2024-03-10T09:26:59Z |
| format | Article |
| id | doaj.art-cda71e097575402696cb1e432abc3636 |
| institution | Directory Open Access Journal |
| issn | 2162-2531 |
| language | English |
| last_indexed | 2024-03-10T09:26:59Z |
| publishDate | 2023-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Nucleic Acids |
| spelling | doaj.art-cda71e097575402696cb1e432abc36362023-11-22T04:47:15ZengElsevierMolecular Therapy: Nucleic Acids2162-25312023-12-0134102074Exosomal miRNA-155-5p from M1-polarized macrophages suppresses angiogenesis by targeting GDF6 to interrupt diabetic wound healingRuohan Lou0Jiali Chen1Fei Zhou2Tian Zhang3Xiuping Chen4Chunming Wang5Bing Guo6Ligen Lin7State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau 999078, ChinaState Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau 999078, ChinaState Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau 999078, ChinaGuizhou Provincial Key Laboratory of Pathogenesis and Drug Research on Common Chronic Diseases, Guizhou Medical University, Guiyang 550025, ChinaState Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau 999078, China; Department of Pharmaceutical Sciences and Technology, Faculty of Health Sciences, University of Macau, Taipa, Macau 999078, ChinaState Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau 999078, China; Department of Pharmaceutical Sciences and Technology, Faculty of Health Sciences, University of Macau, Taipa, Macau 999078, ChinaGuizhou Provincial Key Laboratory of Pathogenesis and Drug Research on Common Chronic Diseases, Guizhou Medical University, Guiyang 550025, ChinaState Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau 999078, China; Department of Pharmaceutical Sciences and Technology, Faculty of Health Sciences, University of Macau, Taipa, Macau 999078, China; Corresponding author: Ligen Lin, State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau 999078, China.Unprogrammed macrophage polarization, especially prolonged activation of proinflammatory macrophages, is associated with delayed wound healing in diabetic objectives. Macrophage-derived exosomes cargo a variety of microRNAs (miRNAs), participating in different stages in wound healing. Here, exosomes were isolated from naive bone marrow–derived macrophages (BMDMs) (M0-Exos), interferon-γ plus lipopolysaccharide-polarized BMDMs (M1-Exos), and interleukin-4-polarized BMDMs (M2-Exos). M1-Exos impaired migration and tube formation in human umbilical vein endothelial cells (HUVECs) compared to M0-Exos, whereas M2-Exos exhibited the opposite effects. High-throughput sequencing was performed to decipher the miRNA expression profiles in M0-Exos, M1-Exos, and M2-Exos. A total of 63 miRNAs were identified to be differentially expressed in exosomes derived from polarized BMDMs. Among them, miRNA-155-5p is highly expressed in M1-Exos, which interrupted angiogenesis in HUVECs. Furthermore, miRNA-155-5p directly binds to the 3′ UTR of growth differentiation factor 6 (GDF6) mRNA to suppress its protein expression. Lastly, local administration of a temperature-sensitive hydrogel Pluronic F-127 loading miRNA-155-5p antagomiR promoted angiogenesis and accelerated wound healing in diabetic db/db mice via enhancing GDF6. In summary, this study deciphered the miRNA expression profiles in exosomes from polarized macrophages. M2-like macrophage-derived exosomes and miRNA-155-5p inhibitors could be promising therapeutics against diabetic foot ulcers.http://www.sciencedirect.com/science/article/pii/S2162253123002925MT: Oligonucleotides: Therapies and Applicationspolarized macrophage-derived exosomesmicroRNA expression profilesdiabetic wound healingangiogenesisgrowth differentiation factor 6 |
| spellingShingle | Ruohan Lou Jiali Chen Fei Zhou Tian Zhang Xiuping Chen Chunming Wang Bing Guo Ligen Lin Exosomal miRNA-155-5p from M1-polarized macrophages suppresses angiogenesis by targeting GDF6 to interrupt diabetic wound healing Molecular Therapy: Nucleic Acids MT: Oligonucleotides: Therapies and Applications polarized macrophage-derived exosomes microRNA expression profiles diabetic wound healing angiogenesis growth differentiation factor 6 |
| title | Exosomal miRNA-155-5p from M1-polarized macrophages suppresses angiogenesis by targeting GDF6 to interrupt diabetic wound healing |
| title_full | Exosomal miRNA-155-5p from M1-polarized macrophages suppresses angiogenesis by targeting GDF6 to interrupt diabetic wound healing |
| title_fullStr | Exosomal miRNA-155-5p from M1-polarized macrophages suppresses angiogenesis by targeting GDF6 to interrupt diabetic wound healing |
| title_full_unstemmed | Exosomal miRNA-155-5p from M1-polarized macrophages suppresses angiogenesis by targeting GDF6 to interrupt diabetic wound healing |
| title_short | Exosomal miRNA-155-5p from M1-polarized macrophages suppresses angiogenesis by targeting GDF6 to interrupt diabetic wound healing |
| title_sort | exosomal mirna 155 5p from m1 polarized macrophages suppresses angiogenesis by targeting gdf6 to interrupt diabetic wound healing |
| topic | MT: Oligonucleotides: Therapies and Applications polarized macrophage-derived exosomes microRNA expression profiles diabetic wound healing angiogenesis growth differentiation factor 6 |
| url | http://www.sciencedirect.com/science/article/pii/S2162253123002925 |
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