|Cancer||Cell death||Cell cycle||Cytoskeleton||Exo/endocytosis||Differentiation||Division||Organelles||Signalling||Stem cells||Trafficking|
Connexin43 promotes survival of mesenchymal stem cells in ischaemic heart
Deguo Wang, Wenzhi Shen, Fengxiang Zhang, Minglong Chen, Hongwu Chen and Kejiang Cao1
Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Guangzhou Road 300, Nanjing, 210029, Peoples Republic of China
The involvement of connexins in regulating cell growth and death has recently been reported. We have investigated whether Cx43 (connexin43) contributes to MSC (mesenchymal stem cell) survival and improves therapeutic efficacy in MI (myocardial infarction). Genetically modified Cx43 MSCs were exposed to hypoxic conditions or injected intramyocardially into a rat MI model. MSCs overexpressing Cx43, with more Bcl-2 and phosphorylated Akt, but less Bax, were relatively tolerant to hypoxic injury. After transplantation, this Cx43 overexpression enhanced cell survival and reduced infarct size, improving contractile performance. Cx43 inhibition by SiRNA reversed the effects of Cx43 overexpression. Therefore, Cx43 may act as a potential target for improving the therapeutic efficacy of MSCs in ischaemic heart disease.
Key words: apoptosis, Bax, Bcl-2, connexin43, mesenchymal stem cells, myocardial infarction
Abbreviations: Ct, threshold cycle, Cx43, connexin43, EF, ejection fraction, FS, fractional shortening, GAPDH, glyceraldehyde-3-phosphate dehydrogenase, GJ, gap junctions, LAD, left anterior descending, MI, myocardial infarction, MSC, mesenchymal stem cells, PI, propidium iodide
1To whom correspondence should be addressed (email kJcao@njmu.edu.cn).
Received 12 August 2009/19 December 2009; accepted 12 January 2010
Published as Cell Biology International Immediate Publication 12 January 2010, doi:10.1042/CBI20090118
© The Author(s) Journal compilation © 2010 Portland Press Limited