Transforming growth factor-β1 promotes contraction of collagen gel by cardiac fibroblasts through their differentiation into myofibroblasts
Transforming growth factor-β1 promotes contraction of collagen gel by cardiac fibroblasts through their differentiation into myofibroblasts
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DOI：
10.1358/mf.2003.25.2.723680
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发表时间：
2003-03-01
影响因子：
--
通讯作者：
Fagard, R
中科院分区：
文献类型：
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作者：
Lijnen, P;Petrov, V;Fagard, R
肌成纤维细胞和转化生长因子-β（TGF-β（1））是心脏组织纤维化发展的关键因素。本研究的目的是确定TGF-β（1）影响心脏成纤维细胞收缩活性的能力是否取决于它们向肌成纤维细胞的分化。因此，将第2代的心脏成纤维细胞（来自雄性成年Wistar大鼠）培养至汇合，并在不含胎牛血清（FBS）的Dulbeccos改良Eagles培养基（DMEM）中，在含和不含TGF-β（1）（0、20、40、100、200、400或600 pmol/l）的水合胶原凝胶上孵育1、2和3天。通过将第二代成纤维细胞在含10%FBS（含或不含TGF-β 1）（0至600 pmol/l）的DMEM中孵育6天，获得心脏成纤维细胞的生长培养物。然后将这些成纤维细胞在胶原凝胶上在不含FBS的DMEM中进一步孵育1、2和3天。TGF-β（1）剂量依赖性地增加由心脏成纤维细胞介导的胶原凝胶收缩，无论是直接加入凝胶中还是在TGF-β（1）存在下培养心脏成纤维细胞6天后，在100 pmol/l TGF-β（1）时达到最大效果。在两种培养条件下，TGF-β（1）也刺激胶原凝胶晶格中心脏成纤维细胞的[H-3]-胸苷掺入和总蛋白含量。在两种培养条件下，TGF-β（1）剂量依赖性地诱导α-平滑肌肌动蛋白（肌成纤维细胞的标志物）的增加。TGF-β 1诱导的胶原凝胶面积减少与TGF-β 1诱导的胶原凝胶基质中α-平滑肌肌动蛋白的出现呈负相关。TGF-β（1）增加成年大鼠心脏成纤维细胞的收缩活性及其分化为肌成纤维细胞的能力。由于收缩活性与分化相关，因此TGF-β 1对心脏成纤维细胞诱导的胶原凝胶收缩的影响可能取决于促进肌成纤维细胞分化。(C)2003年，《科学》杂志。All rights reserved.
Myofibroblasts and transforming growth factor-beta (TGF-beta(1)) are key elements of cardiac tissue fibrosis development. The aim of this study was to determine whether the ability of TGF-beta(1) to affect the contractile activity of cardiac fibroblasts depends on their differentiation into myofibroblasts. Cardiac fibroblasts (from male adult Wistar rats) from passage 2 were therefore cultured to confluency and incubated on a hydrated collagen gel, both with and without TGF-beta(1) (0, 20, 40, 100, 200, 400 or 600 pmol/l), for 1, 2 and 3 days in a Dulbeccos Modified Eagles Medium (DMEM) without fetal bovine serum (FBS). Growing cultures of cardiac fibroblasts were obtained by incubating second-passage fibroblasts in DMEM with 10% FBS with or without TGF-beta(1) (0 to 600 pmol/l) for 6 days. These fibroblasts were then further incubated on the collagen gel for 1, 2 and 3 days in DMEM without FBS. TGF-beta(1) dose-dependently increased the contraction of collagen gel mediated by cardiac fibroblasts, either added directly to the gel or after growing of the cardiac fibroblasts in the presence of TGF-beta(1) for 6 days, reaching a maximal effect at 100 pmol/l TGF-beta(1). In both culturing conditions, TGF-beta(1) also stimulated the [H-3]-thymidine incorporation and the total protein content in the cardiac fibroblasts in the collagen gel lattice. TGF-beta(1) dose-dependently induced an increase in alpha-smooth muscle actin, a marker of myofibroblasts, in both culturing conditions. The TGF-beta(1)-induced reduction of area of the collagen gel was negatively correlated to the TGF-beta(1)-evoked appearance of alpha-smooth muscle actin in the collagen gel matrix. TGF-beta(1) increased the contractile activity of adult rat cardiac fibroblasts and their ability to differentiate into myofibroblasts. Because contractile activity was correlated with differentiation, the influence of TGF-beta(1) on cardiac fibroblast-induced collagen gel contraction may depend on the promotion of myofibroblast differentiation. (C) 2003 Prous Science. All rights reserved.