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Stem Cells International
Volume 2017, Article ID 1096980, 12 pages
Research Article

Hepatoma-Derived Growth Factor Secreted from Mesenchymal Stem Cells Reduces Myocardial Ischemia-Reperfusion Injury

1Department of Cardiology, Second Affiliated Hospital of Zhejiang University School of Medicine, 88 Jiefang Rd, Hangzhou 310009, China
2Cardiovascular Key Laboratory of Zhejiang Province, 88 Jiefang Rd, Hangzhou 310009, China

Correspondence should be addressed to Jian-An Wang; moc.oohay@gnaw_na_naij

Received 25 May 2017; Accepted 4 October 2017; Published 14 November 2017

Academic Editor: Yanfang Chen

Copyright © 2017 Yu Zhou et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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.