Connexin43 promotes survival of mesenchymal stem cells in ischaemic heart.
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.
Wang
Deguo
D
Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Guangzhou Road 300#, Nanjing, 210029, Peoples Republic of China.
Shen
Wenzhi
W
Zhang
Fengxiang
F
Chen
Minglong
M
Chen
Hongwu
H
Cao
Kejiang
K
D000818:Animals; D015687:Cell Hypoxia; D002470:Cell Survival; D018031:Connexin 43 / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D009203:Myocardial Infarction / Q000628:therapy*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering; D051381:Rats; D017207:Rats, Sprague-Dawley
D018031:Connexin 43; D019253:Proto-Oncogene Proteins c-bcl-2; D034741:RNA, Small Interfering; D051057:Proto-Oncogene Proteins c-akt