Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Guangzhou Road 300#, Nanjing, 210029, Peoples Republic of China.
Cell Biol Int. 2010 Mar 12;34(4):415-23. doi: 10.1042/CBI20090118.
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.
间隙连接蛋白(connexins)在调节细胞生长和死亡中的作用最近被报道。我们研究了间隙连接蛋白 43(connexin43,Cx43)是否有助于间充质干细胞(mesenchymal stem cell,MSC)的存活,并提高心肌梗死(myocardial infarction,MI)的治疗效果。将基因修饰的 Cx43 MSC 暴露于低氧环境或注射到大鼠 MI 模型的心肌内。过表达 Cx43 的 MSC 中 Bcl-2 和磷酸化 Akt 增加,而 Bax 减少,对低氧损伤的耐受性相对增强。移植后,这种 Cx43 的过表达增强了细胞存活并减少了梗死面积,改善了收缩功能。Cx43 的 siRNA 抑制逆转了 Cx43 过表达的作用。因此,Cx43 可能成为改善 MSC 在缺血性心脏病治疗效果的潜在靶点。