Hepatoma-Derived Growth Factor Secreted from Mesenchymal Stem Cells Reduces Myocardial Ischemia-Reperfusion Injury
Objectives. The present study aimed to explore the major factors that account for the beneficial effects of mesenchymal stem cells (MSCs). Methods. Using isobaric tags for relative and absolute quantitation method, hepatoma-derived growth factor (HDGF) was identified as an important factor secreted...
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| Format: | Article |
| Language: | English |
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Wiley
2017-01-01
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| Series: | Stem Cells International |
| Online Access: | http://dx.doi.org/10.1155/2017/1096980 |
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| author | Yu Zhou Panpan Chen Qingnian Liu Yingchao Wang Ling Zhang Rongrong Wu Jinghai Chen Hong Yu Wei Zhu Xinyang Hu Jian-An Wang |
| author_facet | Yu Zhou Panpan Chen Qingnian Liu Yingchao Wang Ling Zhang Rongrong Wu Jinghai Chen Hong Yu Wei Zhu Xinyang Hu Jian-An Wang |
| author_sort | Yu Zhou |
| collection | DOAJ |
| description | Objectives. The present study aimed to explore the major factors that account for the beneficial effects of mesenchymal stem cells (MSCs). Methods. Using isobaric tags for relative and absolute quantitation method, hepatoma-derived growth factor (HDGF) was identified as an important factor secreted by MSCs, but not by cardiac fibroblasts (CFs). The protective effects of conditioned medium (CdM) from MSCs or CFs were tested by using either H9C2 cells that were exposed by hypoxia-reoxygenation (H/R) insult or an in vivo mouse model of myocardial ischemia-reperfusion. Results. Compared to CF-CdM, MSC-CdM conferred protection against reperfusion injury. CdM obtained from MSCs that were treated with HDGF-targeted shRNA failed to offer any protection in vitro. In addition, administration of recombinant HDGF alone recapitulated the beneficial effects of MSC-CdM, which was associated with increased protein kinase C epsilon (PKCε) phosphorylation, enhanced mitochondria aldehyde dehydrogenase family 2 activity, and decreased 4-hydroxy-2-nonenal accumulation. A significant decrease in infarct size and ameliorated cardiac dysfunction was achieved by administration of HDGF in wild-type mice, which was absent in PKCε dominant negative mice, indicating the essential roles of PKCε in HDGF-mediated protection. Conclusions. HDGF secreted from MSCs plays a key role in the protection against reperfusion injury through PKCε activation. |
| format | Article |
| id | doaj-art-c433f2d9906545eb9d079b561d8c5c6d |
| institution | OA Journals |
| issn | 1687-966X 1687-9678 |
| language | English |
| publishDate | 2017-01-01 |
| publisher | Wiley |
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| series | Stem Cells International |
| spelling | doaj-art-c433f2d9906545eb9d079b561d8c5c6d2025-08-20T02:18:47ZengWileyStem Cells International1687-966X1687-96782017-01-01201710.1155/2017/10969801096980Hepatoma-Derived Growth Factor Secreted from Mesenchymal Stem Cells Reduces Myocardial Ischemia-Reperfusion InjuryYu Zhou0Panpan Chen1Qingnian Liu2Yingchao Wang3Ling Zhang4Rongrong Wu5Jinghai Chen6Hong Yu7Wei Zhu8Xinyang Hu9Jian-An Wang10Department of Cardiology, Second Affiliated Hospital of Zhejiang University School of Medicine, 88 Jiefang Rd, Hangzhou 310009, ChinaDepartment of Cardiology, Second Affiliated Hospital of Zhejiang University School of Medicine, 88 Jiefang Rd, Hangzhou 310009, ChinaDepartment of Cardiology, Second Affiliated Hospital of Zhejiang University School of Medicine, 88 Jiefang Rd, Hangzhou 310009, ChinaDepartment of Cardiology, Second Affiliated Hospital of Zhejiang University School of Medicine, 88 Jiefang Rd, Hangzhou 310009, ChinaDepartment of Cardiology, Second Affiliated Hospital of Zhejiang University School of Medicine, 88 Jiefang Rd, Hangzhou 310009, ChinaDepartment of Cardiology, Second Affiliated Hospital of Zhejiang University School of Medicine, 88 Jiefang Rd, Hangzhou 310009, ChinaDepartment of Cardiology, Second Affiliated Hospital of Zhejiang University School of Medicine, 88 Jiefang Rd, Hangzhou 310009, ChinaDepartment of Cardiology, Second Affiliated Hospital of Zhejiang University School of Medicine, 88 Jiefang Rd, Hangzhou 310009, ChinaDepartment of Cardiology, Second Affiliated Hospital of Zhejiang University School of Medicine, 88 Jiefang Rd, Hangzhou 310009, ChinaDepartment of Cardiology, Second Affiliated Hospital of Zhejiang University School of Medicine, 88 Jiefang Rd, Hangzhou 310009, ChinaDepartment of Cardiology, Second Affiliated Hospital of Zhejiang University School of Medicine, 88 Jiefang Rd, Hangzhou 310009, ChinaObjectives. The present study aimed to explore the major factors that account for the beneficial effects of mesenchymal stem cells (MSCs). Methods. Using isobaric tags for relative and absolute quantitation method, hepatoma-derived growth factor (HDGF) was identified as an important factor secreted by MSCs, but not by cardiac fibroblasts (CFs). The protective effects of conditioned medium (CdM) from MSCs or CFs were tested by using either H9C2 cells that were exposed by hypoxia-reoxygenation (H/R) insult or an in vivo mouse model of myocardial ischemia-reperfusion. Results. Compared to CF-CdM, MSC-CdM conferred protection against reperfusion injury. CdM obtained from MSCs that were treated with HDGF-targeted shRNA failed to offer any protection in vitro. In addition, administration of recombinant HDGF alone recapitulated the beneficial effects of MSC-CdM, which was associated with increased protein kinase C epsilon (PKCε) phosphorylation, enhanced mitochondria aldehyde dehydrogenase family 2 activity, and decreased 4-hydroxy-2-nonenal accumulation. A significant decrease in infarct size and ameliorated cardiac dysfunction was achieved by administration of HDGF in wild-type mice, which was absent in PKCε dominant negative mice, indicating the essential roles of PKCε in HDGF-mediated protection. Conclusions. HDGF secreted from MSCs plays a key role in the protection against reperfusion injury through PKCε activation.http://dx.doi.org/10.1155/2017/1096980 |
| spellingShingle | Yu Zhou Panpan Chen Qingnian Liu Yingchao Wang Ling Zhang Rongrong Wu Jinghai Chen Hong Yu Wei Zhu Xinyang Hu Jian-An Wang Hepatoma-Derived Growth Factor Secreted from Mesenchymal Stem Cells Reduces Myocardial Ischemia-Reperfusion Injury Stem Cells International |
| title | Hepatoma-Derived Growth Factor Secreted from Mesenchymal Stem Cells Reduces Myocardial Ischemia-Reperfusion Injury |
| title_full | Hepatoma-Derived Growth Factor Secreted from Mesenchymal Stem Cells Reduces Myocardial Ischemia-Reperfusion Injury |
| title_fullStr | Hepatoma-Derived Growth Factor Secreted from Mesenchymal Stem Cells Reduces Myocardial Ischemia-Reperfusion Injury |
| title_full_unstemmed | Hepatoma-Derived Growth Factor Secreted from Mesenchymal Stem Cells Reduces Myocardial Ischemia-Reperfusion Injury |
| title_short | Hepatoma-Derived Growth Factor Secreted from Mesenchymal Stem Cells Reduces Myocardial Ischemia-Reperfusion Injury |
| title_sort | hepatoma derived growth factor secreted from mesenchymal stem cells reduces myocardial ischemia reperfusion injury |
| url | http://dx.doi.org/10.1155/2017/1096980 |
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