Mechanical load enhances the stimulatory effect of serum growth factors on cardiac fibroblast procollagen synthesis
Mechanical load enhances the stimulatory effect of serum growth factors on cardiac fibroblast procollagen synthesis
复制标题
DOI：
10.1006/jmcc.1996.0347
复制
发表时间：
1997-04-01
影响因子：
5
通讯作者：
Bishop, JE
中科院分区：
文献类型：
--
作者：
Butt, RP;Bishop, JE
机械环境是许多组织中细胞活动的关键决定因素。在心血管系统中，它在发育和疾病期间的组织重塑中起作用。在心脏，机械张力的变化刺激心肌细胞肥大和成纤维细胞胶原合成。为了阐明后一种反应的机制，我们确定了机械负荷对心脏成纤维细胞活性的直接影响。在存在或不存在胎牛血清或生长因子的情况下，机械加载胎鼠心脏成纤维细胞的原代培养物，并测定对成纤维细胞复制、前胶原代谢和基因表达的影响。在机械负荷和10%胎牛血清的作用下，48 h前胶原合成比10%胎牛血清对照组增加了99.7 +/- 4.3% （P < 0.01）。前胶原α (1)(I)稳态mRNA水平增加了2倍，在没有血清的情况下没有观察到影响，转化生长因子β 1和胰岛素样生长因子1已被证明可以刺激这些细胞的前胶原代谢。机械负荷增强了对这些生长因子的反应，刺激α (1)(I) mRNA水平分别比单独使用生长因子的对照组高4.3倍和3倍。这些结果表明，机械负荷和促纤维化生长因子对前胶原基因表达和代谢具有协同作用。由于这些因子在心脏肥厚的发展过程中被释放，机械环境和这些多肽之间的相互作用可能为心脏中胶原沉积的增强提供了一种机制。(C) 1997学术出版社有限公司
The mechanical environment is a key determinant of cellular activity in many tissues. In the cardiovascular system it plays a role in tissue remodelling during both development and disease. In the heart changes in mechanical tension stimulate myocyte hypertrophy and fibroblast collagen synthesis. To elucidate the mechanisms for the latter response, we determined the direct effect of mechanical load on cardiac fibroblast activity. Primary cultures of fetal rat cardiac fibroblasts were mechanically loaded in the presence or absence of fetal calf serum or growth factors, and the effects on fibroblast replication and procollagen metabolism and gene expression determined. Procollagen synthesis was increased by 99.7 +/- 4.3% in response to mechanical load and 10% fetal calf serum, compared to 10% fetal calf serum control (P < 0.01) after 48 h. Procollagen alpha(1)(I) steady-state mRNA levels were increased two-fold, No effect was observed in the absence of serum, Transforming growth factor beta 1 and insulinlike growth factor 1 have been demonstrated to stimulate procollagen metabolism by these cells. Mechanical load enhanced the response to these growth factors, stimulating alpha(1)(I) mRNA levels by 4.3 and three-fold, respectively, above growth factor alone controls. These results demonstrate a synergistic effect on procollagen gene expression and metabolism by mechanical load and profibrotic growth factors. Since these factors are released during the development of cardiac hypertrophy, interactions between the mechanical environment and these polypeptides may provide a mechanism for enhanced collagen deposition in the heart. (C) 1997 Academic Press Limited.