Fisher S A, Absher M
Department of Medicine, University of Vermont, Burlington 05405, USA.
Am J Physiol. 1995 Apr;268(4 Pt 1):C910-7. doi: 10.1152/ajpcell.1995.268.4.C910.
Transforming growth factor-beta (TGF-beta) is a ubiquitous growth-regulating protein that is capable of influencing the growth and function of heart cells in vitro. To better understand the role TGF-beta might play as a paracrine mediator of cardiac hypertrophy, the expression, secretion, and growth effects of TGF-beta were examined. Neonatal cardiac fibroblasts in vitro secreted latent TGF-beta 1 and TGF-beta 2 as high as 15 ng/10(6) cells. Angiotensin II (ANG II) and norepinephrine (NE) each augmented up to threefold the expression and secretion of latent TGF-beta 1 and TGF-beta 2 and also induced a shift in isoform predominance from beta 1 to beta 2. Each agent individually produced hypertrophic growth of neonatal cardiocytes and hyperplastic growth of cardiac fibroblasts. Paradoxically, the combination of NE and ANG II at intermediate and high concentrations resulted in less TGF-beta secretion (compared with either agent alone) and in hypertrophic growth of fibroblasts. These results suggest that the growth-promoting effects of ANG II and NE may in part be mediated via a paracrine stimulation of TGF-beta secretion.
转化生长因子-β（TGF-β）是一种普遍存在的生长调节蛋白，能够在体外影响心脏细胞的生长和功能。为了更好地理解TGF-β作为心脏肥大旁分泌介质可能发挥的作用，对TGF-β的表达、分泌和生长效应进行了研究。体外培养的新生心脏成纤维细胞分泌的潜伏型TGF-β1和TGF-β2高达15 ng/10⁶个细胞。血管紧张素II（ANG II）和去甲肾上腺素（NE）各自使潜伏型TGF-β1和TGF-β2的表达和分泌增加了三倍，并且还导致异构体优势从β1向β2转变。每种药物单独作用均可使新生心肌细胞发生肥大性生长，使心脏成纤维细胞发生增生性生长。矛盾的是，中等浓度和高浓度的NE与ANG II联合使用导致TGF-β分泌减少（与单独使用任何一种药物相比），并使成纤维细胞发生肥大性生长。这些结果表明，ANG II和NE的促生长作用可能部分是通过旁分泌刺激TGF-β分泌介导的。
