Ischemic Preconditioning Potentiates the Protective Effect of Stem Cells through Secretion of Exosomes by Targeting Mecp2 via miR-22

被引：380

作者：

Feng, Yuliang ^{[1
,2
]}

Huang, Wei ^{[2
]}

Wani, Mashhood ^{[2
]}

Yu, Xiyong ^{[1
]}

Ashraf, Muhammad ^{[2
]}

机构：

[1] Southern Med Univ, Guangdong Acad Med Sci, Guangdong Prov Cardiovasc Inst, Med Res Ctr,Guangdong Gen Hosp, Guangzhou, Guangdong, Peoples R China

[2] Univ Cincinnati, Dept Pathol & Lab Med, Cincinnati, OH USA

来源：

PLOS ONE | 2014年 / 9卷 / 02期

基金：

美国国家卫生研究院; 中国国家自然科学基金;

关键词：

INFARCTED HEART; SURVIVAL; TRANSPLANTATION; EXPRESSION; REPAIR;

D O I：

10.1371/journal.pone.0088685

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Mesenchymal stem cells (MSCs) have potential application for the treatment of ischemic heart diseases. Besides differentiation properties, MSCs protect ischemic cardiomyocytes by secretion of paracrine factors. In this study, we found exosomes enriched with miR-22 were secreted by MSCs following ischemic preconditioning (Exo(IPC)) and mobilized to cardiomyocytes where they reduced their apoptosis due to ischemia. Interestingly, by time-lapse imaging, we for the first time captured the dynamic shedding of miR-22 loaded exosomes from cytosol to extracellular space. Furthermore, the antiapoptotic effect of miR-22 was mediated by direct targeting of methyl CpG binding protein 2 (Mecp2). In vivo data showed that delivery of Exo(IPC) significantly reduced cardiac fibrosis. Our data identified a significant benefit of Exo(IPC) for the treatment of cardiac diseases by targeting Mecp2 via miR-22.

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页数：8

相关论文

共 19 条

[1] Elevated expression of MeCP2 in cardiac and skeletal tissues is detrimental for normal development [J].

Alvarez-Saavedra, Matias ;

Carrasco, Loreto ;

Sura-Trueba, Sylvia ;

Aiello, Vera Demarchi ;

Walz, Katherina ;

Xavier Neto, Jose ;

Young, Juan I. .

HUMAN MOLECULAR GENETICS, 2010, 19 (11) :2177-2190

[2] Cardiac progenitors derived from reprogrammed mesenchymal stem cells contribute to angiomyogenic repair of the infarcted heart [J].

Buccini, Stephanie ;

Haider, Khawaja Husnain ;

Ahmed, Rafeeq P. H. ;

Jiang, Shujia ;

Ashraf, Muhammad .

BASIC RESEARCH IN CARDIOLOGY, 2012, 107 (06)

[3] Paracrine action accounts for marked protection of ischemic heart by Akt-modified mesenchymal stem cells [J].

Gnecchi, M ;

He, HM ;

Liang, OD ;

Melo, LG ;

Morello, F ;

Mu, H ;

Noiseux, N ;

Zhang, LN ;

Pratt, RE ;

Ingwall, JS ;

Dzau, VJ .

NATURE MEDICINE, 2005, 11 (04) :367-368

[4] Mesenchymal stem cell therapy for heart disease [J].

Gnecchi, Massimiliano ;

Danieli, Patrizia ;

Cervio, Elisabetta .

VASCULAR PHARMACOLOGY, 2012, 57 (01) :48-55

[5] Targeted Deletion of MicroRNA-22 Promotes Stress-Induced Cardiac Dilation and Contractile Dysfunction [J].

Gurha, Priyatansh ;

Abreu-Goodger, Cei ;

Wang, Tiannan ;

Ramirez, Maricela O. ;

Drumond, Ana L. ;

van Dongen, Stijn ;

Chen, Yuqing ;

Bartonicek, Nenad ;

Enright, Anton J. ;

Lee, Brendan ;

Kelm, Robert J., Jr. ;

Reddy, Anilkumar K. ;

Taffet, George E. ;

Bradley, Allan ;

Wehrens, Xander H. ;

Entman, Mark L. ;

Rodriguez, Antony .

CIRCULATION, 2012, 125 (22) :2751-U209

[6] Atheroprotective communication between endothelial cells and smooth muscle cells through miRNAs [J].

Hergenreider, Eduard ;

Heydt, Susanne ;

Treguer, Karine ;

Boettger, Thomas ;

Horrevoets, Anton J. G. ;

Zeiher, Andreas M. ;

Scheffer, Margot P. ;

Frangakis, Achilleas S. ;

Yin, Xiaoke ;

Mayr, Manuel ;

Braun, Thomas ;

Urbich, Carmen ;

Boon, Reinier A. ;

Dimmeler, Stefanie .

NATURE CELL BIOLOGY, 2012, 14 (03) :249-+

[7] MicroRNA-22 Regulates Cardiac Hypertrophy and Remodeling in Response to Stress [J].

Huang, Zhan-Peng ;

Chen, Jinghai ;

Seok, Hee Young ;

Zhang, Zheng ;

Kataoka, Masaharu ;

Hu, Xiaoyun ;

Wang, Da-Zhi .

CIRCULATION RESEARCH, 2013, 112 (09) :1234-U103

[8] Transplantation of Human Pericyte Progenitor Cells Improves the Repair of Infarcted Heart Through Activation of an Angiogenic Program Involving Micro-RNA-132 [J].

Katare, Rajesh ;

Riu, Federica ;

Mitchell, Kathryn ;

Gubernator, Miriam ;

Campagnolo, Paola ;

Cui, Yuxin ;

Fortunato, Orazio ;

Avolio, Elisa ;

Cesselli, Daniela ;

Beltrami, Antonio Paolo ;

Angelini, Gianni ;

Emanueli, Costanza ;

Madeddu, Paolo .

CIRCULATION RESEARCH, 2011, 109 (08) :894-U191

[9] Ischemic Preconditioning Augments Survival of Stem Cells via miR-210 Expression by Targeting Caspase-8-associated Protein 2 [J].

Kim, Ha Won ;

Haider, Husnain K. ;

Jiang, Shujia ;

Ashraf, Muhammad .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2009, 284 (48) :33161-33168

[10] Analysis of circulating microRNA biomarkers in plasma and serum using quantitative reverse transcription-PCR (qRT-PCR) [J].

Kroh, Evan M. ;

Parkin, Rachael K. ;

Mitchell, Patrick S. ;

Tewari, Muneesh .

METHODS, 2010, 50 (04) :298-301