Profibrogenic macrophage-targeted delivery of mitochondrial protector via exosome formula for alleviating pulmonary fibrosis
Pulmonary fibrosis (PF) is a devastating lung disease with limited treatment options. During this pathological process, the profibrogenic macrophage subpopulation plays a crucial role, making the characterization of this subpopulation fundamentally important. The present study revealed a positive co...
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KeAi Communications Co., Ltd.
2024-02-01
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2452199X2300302X |
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| author | Wei Zhang Zhuo Wan Di Qu Wenqi Sun Liang Zhang Yuan Liang Lei Pan Hua Jiang Zichen Ye Mengying Wei Lijun Yuan Guodong Yang Faguang Jin |
| author_facet | Wei Zhang Zhuo Wan Di Qu Wenqi Sun Liang Zhang Yuan Liang Lei Pan Hua Jiang Zichen Ye Mengying Wei Lijun Yuan Guodong Yang Faguang Jin |
| author_sort | Wei Zhang |
| collection | DOAJ |
| description | Pulmonary fibrosis (PF) is a devastating lung disease with limited treatment options. During this pathological process, the profibrogenic macrophage subpopulation plays a crucial role, making the characterization of this subpopulation fundamentally important. The present study revealed a positive correlation between pulmonary macrophages with higher mitochondrial mass (Mømitohigh) and fibrosis. Among the Mømitohigh subpopulation of CD206+ M2, characterized by higher expression of dynamin 1-like (Drp1), as determined by flow cytometry and RNA-seq analysis, a therapeutic intervention was developed using an exosome-based formula composed of pathfinder and therapeutics. A pathfinder exosome called “exosomeMMP19 (ExoMMP19)”, was constructed to display matrix metalloproteinase-19 (MMP19) on the surface to locally break down the excessive extracellular matrix (ECM) in the fibrotic lung. A therapeutic exosome called “exosome therapeutics (ExoTx)”, was engineered to display D-mannose on the surface while encapsulating siDrp1 inside. Prior delivery of ExoMMP19 degraded excessive ECM and thus paved the way for ExoTx to be delivered into Mømitohigh, where ExoTx inhibited mitochondrial fission and alleviated PF. This study has not only identified Mømitohigh as profibrotic macrophages but it has also provided a potent strategy to reverse PF via a combination of formulated exosomes. |
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| spelling | doaj.art-2f97cdc1edb147eaa897b10001c4b1d12024-04-28T10:06:21ZengKeAi Communications Co., Ltd.Bioactive Materials2452-199X2024-02-0132488501Profibrogenic macrophage-targeted delivery of mitochondrial protector via exosome formula for alleviating pulmonary fibrosisWei Zhang0Zhuo Wan1Di Qu2Wenqi Sun3Liang Zhang4Yuan Liang5Lei Pan6Hua Jiang7Zichen Ye8Mengying Wei9Lijun Yuan10Guodong Yang11Faguang Jin12Department of Pulmonary and Critical Care Medicine, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, 710038, ChinaDepartment of Hematology, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, 710038, ChinaDepartment of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, 710032, China; Department of Clinical Pharmacy, General Hospital of Western Theater Command, Chengdu, Sichuan, 610083, ChinaDepartment of Ultrasound Diagnostics, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, 710038, ChinaDepartment of Ultrasound Diagnostics, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, 710038, ChinaDepartment of Ultrasound Diagnostics, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, 710038, ChinaDepartment of Pulmonary and Critical Care Medicine, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, 710038, ChinaDepartment of Pulmonary and Critical Care Medicine, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, 710038, ChinaDepartment of Health Service, Health Service Training Base, Fourth Military Medical University, Xi'an, Shaanxi, 710032, ChinaState Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi'an, Shaanxi, 710032, ChinaDepartment of Ultrasound Diagnostics, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, 710038, ChinaState Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi'an, Shaanxi, 710032, China; Corresponding author. State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, 169th Changlexi Road, Xi'an, Shaanxi, 710032, China.Department of Pulmonary and Critical Care Medicine, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, 710038, China; Corresponding author. Department of Pulmonary and Critical Care Medicine, Tangdu Hospital, Fourth Military Medical University, 1st Xinsi Road, Xi'an, Shaanxi, 710038, China.Pulmonary fibrosis (PF) is a devastating lung disease with limited treatment options. During this pathological process, the profibrogenic macrophage subpopulation plays a crucial role, making the characterization of this subpopulation fundamentally important. The present study revealed a positive correlation between pulmonary macrophages with higher mitochondrial mass (Mømitohigh) and fibrosis. Among the Mømitohigh subpopulation of CD206+ M2, characterized by higher expression of dynamin 1-like (Drp1), as determined by flow cytometry and RNA-seq analysis, a therapeutic intervention was developed using an exosome-based formula composed of pathfinder and therapeutics. A pathfinder exosome called “exosomeMMP19 (ExoMMP19)”, was constructed to display matrix metalloproteinase-19 (MMP19) on the surface to locally break down the excessive extracellular matrix (ECM) in the fibrotic lung. A therapeutic exosome called “exosome therapeutics (ExoTx)”, was engineered to display D-mannose on the surface while encapsulating siDrp1 inside. Prior delivery of ExoMMP19 degraded excessive ECM and thus paved the way for ExoTx to be delivered into Mømitohigh, where ExoTx inhibited mitochondrial fission and alleviated PF. This study has not only identified Mømitohigh as profibrotic macrophages but it has also provided a potent strategy to reverse PF via a combination of formulated exosomes.http://www.sciencedirect.com/science/article/pii/S2452199X2300302XPulmonary fibrosisMacrophagesMitochondrial fissionDrp1Exosomes |
| spellingShingle | Wei Zhang Zhuo Wan Di Qu Wenqi Sun Liang Zhang Yuan Liang Lei Pan Hua Jiang Zichen Ye Mengying Wei Lijun Yuan Guodong Yang Faguang Jin Profibrogenic macrophage-targeted delivery of mitochondrial protector via exosome formula for alleviating pulmonary fibrosis Bioactive Materials Pulmonary fibrosis Macrophages Mitochondrial fission Drp1 Exosomes |
| title | Profibrogenic macrophage-targeted delivery of mitochondrial protector via exosome formula for alleviating pulmonary fibrosis |
| title_full | Profibrogenic macrophage-targeted delivery of mitochondrial protector via exosome formula for alleviating pulmonary fibrosis |
| title_fullStr | Profibrogenic macrophage-targeted delivery of mitochondrial protector via exosome formula for alleviating pulmonary fibrosis |
| title_full_unstemmed | Profibrogenic macrophage-targeted delivery of mitochondrial protector via exosome formula for alleviating pulmonary fibrosis |
| title_short | Profibrogenic macrophage-targeted delivery of mitochondrial protector via exosome formula for alleviating pulmonary fibrosis |
| title_sort | profibrogenic macrophage targeted delivery of mitochondrial protector via exosome formula for alleviating pulmonary fibrosis |
| topic | Pulmonary fibrosis Macrophages Mitochondrial fission Drp1 Exosomes |
| url | http://www.sciencedirect.com/science/article/pii/S2452199X2300302X |
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