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间充质干细胞分泌的肝癌衍生生长因子可减轻心肌缺血再灌注损伤。

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

作者信息

Zhou Yu, Chen Panpan, Liu Qingnian, Wang Yingchao, Zhang Ling, Wu Rongrong, Chen Jinghai, Yu Hong, Zhu Wei, Hu Xinyang, Wang Jian-An

机构信息

Department of Cardiology, Second Affiliated Hospital of Zhejiang University School of Medicine, 88 Jiefang Rd, Hangzhou 310009, China.

Cardiovascular Key Laboratory of Zhejiang Province, 88 Jiefang Rd, Hangzhou 310009, China.

出版信息

Stem Cells Int. 2017;2017:1096980. doi: 10.1155/2017/1096980. Epub 2017 Nov 14.

DOI:10.1155/2017/1096980
PMID:29358952
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5735317/
Abstract

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 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 addition, administration of recombinant HDGF alone recapitulated the beneficial effects of MSC-CdM, which was associated with increased protein kinase C epsilon (PKC) 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 dominant negative mice, indicating the essential roles of PKC in HDGF-mediated protection.

CONCLUSIONS

HDGF secreted from MSCs plays a key role in the protection against reperfusion injury through PKC activation.

摘要

目的

本研究旨在探索间充质干细胞（MSCs）产生有益作用的主要因素。

方法

采用相对与绝对定量的等压标签法，鉴定出肝癌衍生生长因子（HDGF）是MSCs分泌的一种重要因子，而心脏成纤维细胞（CFs）不分泌该因子。通过使用经缺氧复氧（H/R）损伤处理的H9C2细胞或心肌缺血再灌注小鼠模型，测试了MSCs或CFs的条件培养基（CdM）的保护作用。

结果

与CF-CdM相比，MSC-CdM对再灌注损伤具有保护作用。从用HDGF靶向短发夹RNA处理的MSCs获得的CdM未能提供任何保护作用。此外，单独给予重组HDGF可重现MSC-CdM的有益作用，这与蛋白激酶Cε（PKC）磷酸化增加、线粒体乙醛脱氢酶家族2活性增强以及4-羟基-2-壬烯醛积累减少有关。在野生型小鼠中给予HDGF可使梗死面积显著减小并改善心脏功能障碍，而在PKC显性阴性小鼠中则不存在这种情况，这表明PKC在HDGF介导的保护作用中起重要作用。

结论

MSCs分泌的HDGF通过激活PKC在抗再灌注损伤中起关键作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6283/5735317/8460d12c364f/SCI2017-1096980.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6283/5735317/0bbdbc1fb8bd/SCI2017-1096980.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6283/5735317/96520a52fd91/SCI2017-1096980.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6283/5735317/504673fad1ca/SCI2017-1096980.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6283/5735317/87cca4d24f3c/SCI2017-1096980.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6283/5735317/8460d12c364f/SCI2017-1096980.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6283/5735317/0bbdbc1fb8bd/SCI2017-1096980.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6283/5735317/96520a52fd91/SCI2017-1096980.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6283/5735317/504673fad1ca/SCI2017-1096980.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6283/5735317/87cca4d24f3c/SCI2017-1096980.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6283/5735317/8460d12c364f/SCI2017-1096980.005.jpg

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