期刊
STEM CELLS INTERNATIONAL
卷 2017, 期 -, 页码 -出版社
HINDAWI LTD
DOI: 10.1155/2017/1096980
关键词
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资金
- National High-tech RD 863 Program [2013AA020101]
- National Basic Research Program of China (973 Program) [2014CB965100, 2014CB965103]
- National Natural Science Foundation of China [31171418, 81320108003, 31371498, 81170308, 81370247, 81573641, 31271585, 81370346]
- Science and Technology Department of Zhejiang Province public welfare projects [2013C37054, 2014C33190]
- Zhejiang Provincial Natural Science Foundation [LY16H280003, 2013C24009]
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 (PKC epsilon) 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 PKC epsilon dominant negative mice, indicating the essential roles of PKC epsilon in HDGF-mediated protection. Conclusions. HDGF secreted from MSCs plays a key role in the protection against reperfusion injury through PKC epsilon activation.
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