Persistence of TGF-β1 induction of increased fibroblast contractility
Persistence of TGF-β1 induction of increased fibroblast contractility
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DOI：
10.1290/1071-2690(2001)037
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发表时间：
2001-03-01
影响因子：
2.1
通讯作者：
Rennard, SI
中科院分区：
文献类型：
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作者：
Liu, XD;Umino, T;Rennard, SI
胶原凝胶的成纤维细胞收缩被认为是伤口收缩的一种模型。在这种凝胶中加入转化生长因子(转化生长因子)-β可以增强收缩，这与其作为纤维化修复介质的作用是一致的。由于从纤维组织分离的成纤维细胞被认为表达“纤维化表型”，我们假设转化生长因子-β暴露可能导致成纤维细胞收缩能力的持续增加。为了评估这一问题，将融合的人胎肺成纤维细胞用无血清的Dulbecco改良Eagle培养液(DMEM)处理48h，分别加入或不加100 nM的转化生长因子-β1、转化生长因子-β2或转化生长因子-β3，然后将成纤维细胞胰酶消化，制成天然的鼠尾肌腱I型胶原凝胶。FBR凝胶化20min后，凝胶释放并保存在无血清DMEM中。经转化生长因子-β处理的成纤维细胞引起显著更快的凝胶收缩(52.5+/-0.6。经转化生长因子-β1、-β2和-β3处理的成纤维细胞分别为50.9+/-0.2和50.3+/-0.5%，而对照组为74.0+/-0.3%(P<0.01)。这种效应是浓度依赖的(50-200 nM)，并且三种异构体具有相同的活性。然而，在去除转化生长因子-β后，转化生长因子-1的作用只持续了很短一段时间，并随着连续传代而消失。这些观察结果表明，纤维组织成纤维细胞介导的胶原-凝胶收缩能力的持续增加，似乎不仅仅是因为这些细胞先前暴露于转化生长因子-β。
Fibroblast contraction of collagen gels is regarded as a model of wound contraction. Transforming growth factor (TGF)-beta added to such gels can augment contraction consistent with its suggested role as a mediator of fibrotic repair. Since fibroblasts isolated from fibrotic tissues have been suggested to express a "fibrotic phenotype," we hypothesized that TGF-beta exposure may lead to a persistent increase in fibroblasts' contractility. To evaluate this question, confluent human fetal lung fibroblasts were treated with serum-free Dulbecco modified Eagle medium (DMEM), with or without 100 nM TGF-beta1, TGF-beta2, or TGF-beta3 for 48 h. Fibroblasts were then trypsinized and cast into gels composed of native type I collagen isolated from rat tail tendons. After 20 min fbr gelation, the gels were released and maintained in serum-free DMEM. TGF-beta -pretreated fibroblasts caused significantly more rapid gel contraction (52.5 +/- 0.6. 50.9 +/- 0.2, and 50.3 +/- 0.5% by TGF-beta1, -beta2, and -beta3 pretreated fibroblasts, respectively) than control fibroblasts (74.0 +/- 0.3%, P < 0.01). This effect is concentration dependent (50-200 nM), and all three isoforms had equal activity. The effect of TGF-1, however, persisted for only a short period of time following the removal of TGF-beta, and was lost with sequential passage. These observations suggest that the persistent increase in collagen-gel contractility mediated hy fibroblasts from fibrotic tissues, would not appear to he solely due to previous exposure of these cells to TGF-beta.