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Int J Mol Sci. 2016 Oct 20;17(10). pii: E1752.

MicroRNA-Mediated Down-Regulation of Apoptosis Signal-Regulating Kinase 1 (ASK1) Attenuates the Apoptosis of Human Mesenchymal Stem Cells (MSCs) Transplanted into Infarcted Heart.

Author information

1
Department of Integrated Omics for Biomedical Sciences, Yonsei University, 03722 Seoul, Korea. cylee083@gmail.com.
2
Department of Integrated Omics for Biomedical Sciences, Yonsei University, 03722 Seoul, Korea. ssh5043@naver.com.
3
Brain Korea 21 PLUS Project for Medical Science, Yonsei University, 03722 Seoul, Korea. jylee12@yuhs.ac.
4
Brain Korea 21 PLUS Project for Medical Science, Yonsei University, 03722 Seoul, Korea. shh17@yuhs.ac.
5
Department of Veterinary Medicine, Chonbuk National University, 54896 Jeonju, Korea. gurrygurry@naver.com.
6
Department of Integrated Omics for Biomedical Sciences, Yonsei University, 03722 Seoul, Korea. kimhyaemin17@gmail.com.
7
Institute for Bio-Medical Convergence, College of Medicine, Catholic Kwandong University, Gangneung, 25601 Gangwon-do, Korea. gardenia@hanmail.net.
8
Institute for Bio-Medical Convergence, College of Medicine, Catholic Kwandong University, Gangneung, 25601 Gangwon-do, Korea. doctor7408@gmail.com.
9
Institute for Bio-Medical Convergence, College of Medicine, Catholic Kwandong University, Gangneung, 25601 Gangwon-do, Korea. sam1017@ish.ac.kr.
10
Catholic Kwandong University, International St. Mary's Hospital, 22711 Incheon, Korea. sam1017@ish.ac.kr.
11
Institute for Bio-Medical Convergence, College of Medicine, Catholic Kwandong University, Gangneung, 25601 Gangwon-do, Korea. slim724@cku.ac.kr.
12
Catholic Kwandong University, International St. Mary's Hospital, 22711 Incheon, Korea. slim724@cku.ac.kr.
13
Institute for Bio-Medical Convergence, College of Medicine, Catholic Kwandong University, Gangneung, 25601 Gangwon-do, Korea. kchwang@cku.ac.kr.
14
Catholic Kwandong University, International St. Mary's Hospital, 22711 Incheon, Korea. kchwang@cku.ac.kr.

Abstract

Stem cell therapy using adult stem cells, such as mesenchymal stem cells (MSCs) has produced some promising results in treating the damaged heart. However, the low survival rate of MSCs after transplantation is still one of the crucial factors that limit the therapeutic effect of stem cells. In the damaged heart, oxidative stress due to reactive oxygen species (ROS) production can cause the death of transplanted MSCs. Apoptosis signal-regulating kinase 1 (ASK1) has been implicated in the development of oxidative stress-related pathologic conditions. Thus, we hypothesized that down-regulation of ASK1 in human MSCs (hMSCs) might attenuate the post-transplantation death of MSCs. To test this hypothesis, we screened microRNAs (miRNAs) based on a miRNA-target prediction database and empirical data and investigated the anti-apoptotic effect of selected miRNAs on human adipose-derived stem cells (hASCs) and on rat myocardial infarction (MI) models. Our data indicated that miRNA-301a most significantly suppressed ASK1 expression in hASCs. Apoptosis-related genes were significantly down-regulated in miRNA-301a-enriched hASCs exposed to hypoxic conditions. Taken together, these data show that miRNA-mediated down-regulation of ASK1 protects MSCs during post-transplantation, leading to an increase in the efficacy of MSC-based cell therapy.

KEYWORDS:

adipose-derived stem cell (ASC); apoptosis signal-regulating kinase 1 (ASK1); mesenchymal stem cells (MSCs); microRNA-301a; myocardial infarction (MI); reactive oxygen species (ROS)

PMID:
27775615
PMCID:
PMC5085777
DOI:
10.3390/ijms17101752
[Indexed for MEDLINE]
Free PMC Article

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