Exosomes Derived from Mesenchymal Stem Cells Ameliorate Hypoxia/Reoxygenation-Injured ECs via Transferring MicroRNA-126
Mesenchymal stem cells (MSCs) show protective effects on ischemia/reperfusion- (I/R-) induced endothelial cell (EC) injury and vascular damage. Stem cell-released exosomes (EXs) could modulate target cell functions by delivering their cargos, and exert therapeutic effects as their mother cells. miR-...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2019-01-01
|
| Series: | Stem Cells International |
| Online Access: | http://dx.doi.org/10.1155/2019/2831756 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832548891219722240 |
|---|---|
| author | Qunwen Pan Yan Wang Qing Lan Weiquan Wu Zhenxuan Li Xiaotang Ma Liming Yu |
| author_facet | Qunwen Pan Yan Wang Qing Lan Weiquan Wu Zhenxuan Li Xiaotang Ma Liming Yu |
| author_sort | Qunwen Pan |
| collection | DOAJ |
| description | Mesenchymal stem cells (MSCs) show protective effects on ischemia/reperfusion- (I/R-) induced endothelial cell (EC) injury and vascular damage. Stem cell-released exosomes (EXs) could modulate target cell functions by delivering their cargos, and exert therapeutic effects as their mother cells. miR-126 is an important regulator of EC functions and angiogenesis. In this study, we determined whether EXs released from MSC-EXs provided beneficial effects on hypoxia/reoxygenation- (H/R-) injured ECs by transferring miR-126. MSCs were transfected with a miR-126 mimic or miR-126 short hairpin RNA to obtain miR-126-overexpressing MSC-EXs (MSC-EXsmiR-126) and miR-126 knockdown MSC-EXs (MSC-EXsSimiR-126). For functional studies, H/R-injured ECs were coincubated with various MSC-EXs. The viability, migration, tube formation ability, and apoptosis of ECs were measured. miR-126 and proangiogenic/growth factor (VEGF, EGF, PDGF, and bFGF) expressions were detected by qRT-PCR. Akt, p-Akt, p-eNOS, and cleaved caspase-3 expressions were examined by western blot. The PI3K inhibitor (LY294002) was used in pathway analysis. We found that overexpression/knockdown of miR-126 increased/decreased the proliferation of MSCs, as well as miR-126 expression in their derived MSC-EXs. MSC-EXsmiR-126 were more effective in promoting proliferation, migration, and tube formation ability of H/R-injured ECs than MSC-EXs. These effects were associated with the increase in p-Akt/Akt and p-eNOS, which could be abolished by LY294002. Besides, MSC-EXsmiR-126 were more effective than MSC-EXs in reducing the apoptosis of ECs, coupled with the decrease in cleaved caspase-3. Moreover, compared to MSC-EXs, MSC-EXsmiR-126 significantly upregulated the level of VEGF, EGF, PDGF, and bFGF in H/R-injured ECs. Downregulation of miR-126 in MSC-EXs inhibited these effects of MSC-EXs. The results suggest that MSC-EXs could enhance the survival and angiogenic function of H/R-injured ECs via delivering miR-126 to ECs and subsequently activate the PI3K/Akt/eNOS pathway, decrease cleaved caspase-3 expression, and increase angiogenic and growth factors. |
| format | Article |
| id | doaj-art-6f31d50f7e5643dea11e400cb442b59e |
| institution | Kabale University |
| issn | 1687-966X 1687-9678 |
| language | English |
| publishDate | 2019-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Stem Cells International |
| spelling | doaj-art-6f31d50f7e5643dea11e400cb442b59e2025-02-03T06:12:48ZengWileyStem Cells International1687-966X1687-96782019-01-01201910.1155/2019/28317562831756Exosomes Derived from Mesenchymal Stem Cells Ameliorate Hypoxia/Reoxygenation-Injured ECs via Transferring MicroRNA-126Qunwen Pan0Yan Wang1Qing Lan2Weiquan Wu3Zhenxuan Li4Xiaotang Ma5Liming Yu6Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Institute of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, ChinaGuangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Institute of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, ChinaDepartment of Stomatology, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, ChinaGuangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Institute of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, ChinaDepartment of Stomatology, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, ChinaGuangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Institute of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, ChinaDepartment of Stomatology, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, ChinaMesenchymal stem cells (MSCs) show protective effects on ischemia/reperfusion- (I/R-) induced endothelial cell (EC) injury and vascular damage. Stem cell-released exosomes (EXs) could modulate target cell functions by delivering their cargos, and exert therapeutic effects as their mother cells. miR-126 is an important regulator of EC functions and angiogenesis. In this study, we determined whether EXs released from MSC-EXs provided beneficial effects on hypoxia/reoxygenation- (H/R-) injured ECs by transferring miR-126. MSCs were transfected with a miR-126 mimic or miR-126 short hairpin RNA to obtain miR-126-overexpressing MSC-EXs (MSC-EXsmiR-126) and miR-126 knockdown MSC-EXs (MSC-EXsSimiR-126). For functional studies, H/R-injured ECs were coincubated with various MSC-EXs. The viability, migration, tube formation ability, and apoptosis of ECs were measured. miR-126 and proangiogenic/growth factor (VEGF, EGF, PDGF, and bFGF) expressions were detected by qRT-PCR. Akt, p-Akt, p-eNOS, and cleaved caspase-3 expressions were examined by western blot. The PI3K inhibitor (LY294002) was used in pathway analysis. We found that overexpression/knockdown of miR-126 increased/decreased the proliferation of MSCs, as well as miR-126 expression in their derived MSC-EXs. MSC-EXsmiR-126 were more effective in promoting proliferation, migration, and tube formation ability of H/R-injured ECs than MSC-EXs. These effects were associated with the increase in p-Akt/Akt and p-eNOS, which could be abolished by LY294002. Besides, MSC-EXsmiR-126 were more effective than MSC-EXs in reducing the apoptosis of ECs, coupled with the decrease in cleaved caspase-3. Moreover, compared to MSC-EXs, MSC-EXsmiR-126 significantly upregulated the level of VEGF, EGF, PDGF, and bFGF in H/R-injured ECs. Downregulation of miR-126 in MSC-EXs inhibited these effects of MSC-EXs. The results suggest that MSC-EXs could enhance the survival and angiogenic function of H/R-injured ECs via delivering miR-126 to ECs and subsequently activate the PI3K/Akt/eNOS pathway, decrease cleaved caspase-3 expression, and increase angiogenic and growth factors.http://dx.doi.org/10.1155/2019/2831756 |
| spellingShingle | Qunwen Pan Yan Wang Qing Lan Weiquan Wu Zhenxuan Li Xiaotang Ma Liming Yu Exosomes Derived from Mesenchymal Stem Cells Ameliorate Hypoxia/Reoxygenation-Injured ECs via Transferring MicroRNA-126 Stem Cells International |
| title | Exosomes Derived from Mesenchymal Stem Cells Ameliorate Hypoxia/Reoxygenation-Injured ECs via Transferring MicroRNA-126 |
| title_full | Exosomes Derived from Mesenchymal Stem Cells Ameliorate Hypoxia/Reoxygenation-Injured ECs via Transferring MicroRNA-126 |
| title_fullStr | Exosomes Derived from Mesenchymal Stem Cells Ameliorate Hypoxia/Reoxygenation-Injured ECs via Transferring MicroRNA-126 |
| title_full_unstemmed | Exosomes Derived from Mesenchymal Stem Cells Ameliorate Hypoxia/Reoxygenation-Injured ECs via Transferring MicroRNA-126 |
| title_short | Exosomes Derived from Mesenchymal Stem Cells Ameliorate Hypoxia/Reoxygenation-Injured ECs via Transferring MicroRNA-126 |
| title_sort | exosomes derived from mesenchymal stem cells ameliorate hypoxia reoxygenation injured ecs via transferring microrna 126 |
| url | http://dx.doi.org/10.1155/2019/2831756 |
| work_keys_str_mv | AT qunwenpan exosomesderivedfrommesenchymalstemcellsamelioratehypoxiareoxygenationinjuredecsviatransferringmicrorna126 AT yanwang exosomesderivedfrommesenchymalstemcellsamelioratehypoxiareoxygenationinjuredecsviatransferringmicrorna126 AT qinglan exosomesderivedfrommesenchymalstemcellsamelioratehypoxiareoxygenationinjuredecsviatransferringmicrorna126 AT weiquanwu exosomesderivedfrommesenchymalstemcellsamelioratehypoxiareoxygenationinjuredecsviatransferringmicrorna126 AT zhenxuanli exosomesderivedfrommesenchymalstemcellsamelioratehypoxiareoxygenationinjuredecsviatransferringmicrorna126 AT xiaotangma exosomesderivedfrommesenchymalstemcellsamelioratehypoxiareoxygenationinjuredecsviatransferringmicrorna126 AT limingyu exosomesderivedfrommesenchymalstemcellsamelioratehypoxiareoxygenationinjuredecsviatransferringmicrorna126 |