MacLellan W R, Brand T, Schneider M D
Department of Medicine, Baylor College of Medicine, Houston, Tex. 77030.
Circ Res. 1993 Nov;73(5):783-91. doi: 10.1161/01.res.73.5.783.
The transforming growth factor-beta (TGF-beta) superfamily comprises a set of regulatory peptides with multiple effects on cell growth and differentiation. The elaborate regulation of TGF-beta s during embryonic development of the heart, the upregulation of TGF-beta after hemodynamic stress, and the impact of TGF-beta on cardiac gene expression together imply a prominent functional role for this family of growth factors in cardiac organogenesis and hypertrophy. Basal and TGF-beta-induced expression of skeletal alpha-actin, one of several genes specifically associated with developing or hypertrophied myocardium, each are contingent on transcriptional activation by serum response factor. A truncated form of the type II TGF-beta receptor, created by deletion of the cytoplasmic kinase domain, acts as a dominant suppressor of TGF-beta signal transduction in cultured cardiac muscle cells and may provide a suitable means to establish the functions of TGF-beta in vivo.
转化生长因子-β(TGF-β)超家族由一组对细胞生长和分化具有多种作用的调节肽组成。在心脏胚胎发育过程中对TGF-β进行精细调节、血流动力学应激后TGF-β的上调以及TGF-β对心脏基因表达的影响,共同表明该生长因子家族在心脏器官发生和肥大中具有重要的功能作用。骨骼肌α-肌动蛋白是与发育中的或肥大的心肌特异性相关的几个基因之一,其基础表达和TGF-β诱导的表达均取决于血清反应因子的转录激活。通过缺失细胞质激酶结构域产生的II型TGF-β受体的截短形式,在培养的心肌细胞中作为TGF-β信号转导的显性抑制剂,可能为在体内确定TGF-β的功能提供合适的手段。