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Stem cell factor/c-kit signaling mediated cardiac stem cell migration via activation of p38 MAPK

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Basic Research in Cardiology Aims and scope Submit manuscript

Abstract

Objective

It was reported that there are cardiac stem cells (CSCs) in the rat heart, and they could reconstitute well-differentiated myocardium that are formed by blood-carrying new vessels and myocytes. However, how do the CSCs migrate into the peri-infarcted areas after myocardial infarction (MI)? It remains entirely unknown about the signal transduction involved in the migration of CSCs.

Methods and results

Rat heart MI was induced by left coronary artery ligation. Both immunohistochemical staining and Western blotting analysis was performed to detect the expression of SCF protein, and RT-PCR was conducted for the expression of SCF mRNA. Cardiac stem cells were isolated from rat hearts, and a cardiac stem cell migration assay was performed using a 48-well chemotaxis chamber system. On day 5 after MI in rats, the expression of stem cell factor (SCF) mRNA and protein was significantly increased in the peri-infarcted area, which was matched with more accumulation of CSCs in the region and improvement of cardiac function, which was blocked by p38 MAPK selective inhibitor SB203580. In in vitro experiments, SCF induced CSC migration in a concentration-dependent manner, and the antibody against SCF receptor (c-kit) blocked the SCF-induced CSC migration. Western blot analysis showed that the phosphorylated p38 MAPK (Phospho-p38 MAPK) was highly increased in the SCF-treated CSCs, and the inhibition of p38 MAPK activity significantly attenuated SCF-induced the migration of CSCs.

Conclusion

It demonstrated that SCF/c-kit signaling may mediate the migration of CSCs via activation of p38 MAPK.

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Acknowledgements

This study was supported in part by research grants 30470710 from the National Natural Science Foundation of China, NCET-04-0711 from the Program for New Century Excellent Talents in University, and 2005ABB009 from the Natural Science Foundation of Hubei.

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Authors and Affiliations

  1. Institute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, 430030, People’s Republic of China

    Dong Kuang, Xia Zhao, Guixiang Xiao, Juan Ni, Renliang Wu & Guoping Wang

  2. Dept. of Biochemistry, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

    Youmei Feng

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  1. Dong Kuang
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  2. Xia Zhao
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  3. Guixiang Xiao
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  7. Guoping Wang
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Correspondence to Guoping Wang.

Additional information

Returned for 1. Revision: 22 August 2007 1. Revision received: 11 October 2007

Returned for 2. Revision: 31 October 2007 2. Revision received: 2 November 2007

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Kuang, D., Zhao, X., Xiao, G. et al. Stem cell factor/c-kit signaling mediated cardiac stem cell migration via activation of p38 MAPK. Basic Res Cardiol 103, 265–273 (2008). https://doi.org/10.1007/s00395-007-0690-z

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  • DOI: https://doi.org/10.1007/s00395-007-0690-z

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