Plasminogen regulates mesenchymal stem cell–mediated tissue repair after ischemia through Cyr61 activation
Autor: | Ling Qin, Yanling Wang, Yanqing Gong, Yi Fan, Maohuan Lin, Hongyu Han, Hyun Jun Kim, Hao Duan, R. Alan Mitteer, Fan Yang, Zhenqiang He, Eujing Yeo |
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Rok vydání: | 2020 |
Předmět: |
Male
0301 basic medicine medicine.medical_treatment Plasmin Ischemia Neovascularization Physiologic Mesenchymal Stem Cell Transplantation Neovascularization Mice 03 medical and health sciences Paracrine signalling 0302 clinical medicine Vascular Biology medicine Animals Mice Knockout business.industry Mesenchymal stem cell Stem cell transplantation Mesenchymal Stem Cells Plasminogen General Medicine medicine.disease Hindlimb Mice Inbred C57BL Endothelial stem cell Transplantation Disease Models Animal 030104 developmental biology Cytokine 030220 oncology & carcinogenesis Cancer research Female medicine.symptom Stem cell business Cysteine-Rich Protein 61 Research Article |
Zdroj: | JCI Insight |
ISSN: | 2379-3708 |
DOI: | 10.1172/jci.insight.131376 |
Popis: | Stem cell transplantation has emerged as a promising strategy in regenerative medicine. However, the poor survival and persistence of the transplanted cells, including mesenchymal stem cells (MSCs), in the hostile ischemic microenvironments represents a major therapeutic barrier. Here we report that plasminogen (Plg) stimulated MSC functions and promoted MSC survival during tissue repair after ischemia. Genetic Plg ablation abolished MSC survival, migration, and proliferation in mouse ischemic limbs, and abrogated MSC-mediated blood reperfusion, neovascularization, and tissue repair after ischemia, suggesting a critical role for Plg in MSC-mediated tissue repair. Furthermore, multiplex cytokine array analysis identified that Plg cleaved and activated cysteine-rich protein 61 (Cyr61), an ECM-associated growth factor, to stimulate MSC survival and migration. Overexpression with truncated Cyr61 in MSCs rescued blood reperfusion after hind limb ischemia in Plg-deficient mice. Finally, Plg-mediated Cyr61 cleavage promoted endothelial cell migration and neovascularization in vitro and in vivo. Our study reveals that Plg promotes MSC survival, persistence, and paracrine effects and improves postischemic neovascularization and tissue repair through Cyr61 cleavage and activation. Thus, targeting Plg/Cyr61 may offer exciting therapeutic opportunities for strengthening MSC therapy in ischemic diseases. Plasminogen promotes mesenchymal stem cell function and improves post-ischemic neovascularization and tissue repair through cysteine-rich protein 61 activation. |
Databáze: | OpenAIRE |
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