Neuregulin-1b1; and b2; isoform expression in cardiac microvascular endothelial cells and function in cardiac myocytes in vitro
- 作者：Gregory M. Cote ; Thomas A. Miller ; Nathan K. LeBrasseur ; Yukio Kuramochi and Douglas B. Sawyer
- 关键词：Neuregulin ; erbB2 ; Cardiac microvascular endothelial cell ; Cardiac myocyte
- 刊名：Experimental Cell Research
- 出版年：2005
- 期刊代码：292_00144827
- 类别：med
- 出版时间：2005
- 卷：311
- 期：1
- 页码：135-146
- 文件大小：556 K
摘要
Neuregulins (NRGs) are a family of alternatively spliced growth factors that act through receptor tyrosine kinases of the epidermal growth factor (EGF) receptor family in diverse tissues. The NRG-erbB signaling axis is a critical mediator of cardiac development, and growing evidence supports a role for this system in the intricate cross-talk between the microvascular endothelium and myocytes in the adult heart. The purpose of this study was first to examine the expression of splice variants of the NRG1 gene in adult rat cardiac microvascular endothelial cells and second to compare the function of these variants in cardiac myocytes. We demonstrate that cardiac microvascular endothelial cells in rat culture express multiple Type I NRG1 gene products, including both b1; and b2; variants. Comparison of the activity of recombinant NRG1b1; and NRG1b2; EGF-like domain proteins in cardiac myocytes shows that the b2; ligand is a more potent activator of receptor phosphorylation and intracellular signaling than the b1; ligand, and only the b2; ligand stimulated glucose uptake and protein synthesis in these culture conditions. Thus, cardiac microvascular endothelial cells express multiple NRG1 isotypes, but only b2;-variants are biologically active on cardiac myocytes.