Regulation of proliferative response of cardiac fibroblasts by transforming growth factor-beta 1.
Regulation of proliferative response of cardiac fibroblasts by transforming growth factor-beta 1.
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DOI：
10.1006/jmcc.1996.0185
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发表时间：
1996-09
影响因子：
5
通讯作者：
A. Sigel;M. Centrella;M. Eghbali-Webb
中科院分区：
文献类型：
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作者：
A. Sigel;M. Centrella;M. Eghbali-Webb
心脏成纤维细胞占心脏中非肌细胞的90%以上。以前，已经确定心脏成纤维细胞倾向于转化为具有肌肉特异性特征的表型，并且转化生长因子-β 1（TGF-β 1）是该事件的特异性诱导剂。在这项研究中，假设TGF-β 1诱导的心脏成纤维细胞的表型调制与其改变的增殖能力进行了测试。因此，在正常的细胞培养条件下，并在一个有效的有丝分裂原，碱性成纤维细胞生长因子（bFGF）的反应，TGF-β 1对心脏成纤维细胞的DNA合成的影响进行了测定。结果表明，15 ng/ml（诱导成纤维细胞“转化”的浓度）的TGF-β 1对心脏成纤维细胞的增殖能力具有调节作用，这种增殖能力随着培养物中细胞密度的变化而变化。在亚汇合和汇合培养物中，用TGF-β 1预处理心脏成纤维细胞24小时导致bFGF诱导的DNA合成刺激发生显著变化。TGF-β 1诱导的心肌成纤维细胞DNA合成的抑制与其表型调节一致，这一点通过肌节肌动蛋白mRNA的表达和形态学变化来证明。用[125 I]标记的TGF-β 1进行的交联研究表明，在实验条件下，心脏成纤维细胞上存在常规的I、II和III型TGF-β 1受体复合物及其与TGF-β 1的结合。总之，这些数据表明心脏成纤维细胞的增殖能力受TGF-β 1控制。他们进一步表明，TGF-β 1诱导的心脏成纤维细胞的表型调节可能会扩展到包括其改变的增殖能力。
Cardiac fibroblasts constitute greater than 90% of the non-myocyte cells in the heart. Previously, it was established that cardiac fibroblasts are predisposed to transformation into a phenotype with muscle-specific features and that transforming growth factor-beta 1 (TGF-beta 1) is a specific inducer of this event. In this study the hypothesis that TGF-beta 1-induced phenotypic modulation of cardiac fibroblasts is associated with their altered proliferative capacity is tested. Therefore the effects of TGF-beta 1 on DNA synthesis in cardiac fibroblasts under normal conditions of cell culture and in response to a potent mitogen, basic fibroblasts growth factor (bFGF) were determined. The results showed that TGF-beta 1 at 15 ng/ml (a concentration that induces fibroblast "transformation") had a regulatory effect on proliferative capacity of cardiac fibroblasts which varied as the function of cell density in culture. In subconfluent and confluent cultures, pre-treatment of cardiac fibroblasts with TGF-beta 1 for 24 h resulted in a dramatic shift in the bFGF-induced stimulation of DNA synthesis. TGF-beta 1-induced inhibition of DNA synthesis in cardiac fibroblasts coincided with their phenotypic modulation as evidenced by the expression of sarcomeric actin mRNA and morphological changes. Cross-linking studies with [125I]-labeled TGF-beta 1 showed the presence of conventional types I, II and III TGF-beta 1 receptor complexes on cardiac fibroblasts and their binding to TGF-beta 1 under the experimental conditions. In summary, these data indicate that the proliferative capacity of cardiac fibroblasts is controlled by TGF-beta 1. They further suggest that the TGF-beta 1-induced phenotypic modulation of cardiac fibroblasts may be extended to include their altered proliferative capacity.