Lijnen Paul, Petrov Victor, Fagard Robert
Hypertension Unit, Campus Gasthuisberg, Leuven, B-3000, Belgium.
J Renin Angiotensin Aldosterone Syst. 2003 Jun;4(2):113-8. doi: 10.3317/jraas.2003.011.
Myofibroblasts and transforming growth factor-beta(1) (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 two were cultured to confluency and incubated on a hydrated collagen gel with and without TGF-beta(1) (0, 20, 40, 100, 200, 400 or 600 pmol/L) for one, two and three days in a Dulbecco's Modified Eagle's Medium without foetal bovine serum.
TGF-beta(1) dose-dependently increased the contraction of collagen gel mediated by cardiac fibroblasts, reaching a maximal effect at 100 pmol/L TGF-beta(1). TGF-beta(1) also stimulated 3(H)-thymidine incorporation and total protein content in cardiac fibroblasts in the collagen gel lattice. TGF-beta(1) dose-dependently induced an increase in beta-smooth muscle actin, a marker of myofibroblasts. The TGF-beta(1)-induced reduction of area of the collagen gel was negatively correlated to the TGF-beta(1)-evoked appearance of a-smooth muscle actin in the collagen gel matrix.
Our data demonstrate that 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 might depend on the promotion of myofibroblast differentiation.
肌成纤维细胞和转化生长因子-β1（TGF-β1）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-β1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。
将传代两代的心脏成纤维细胞（来自成年雄性Wistar大鼠）培养至汇合，在不含胎牛血清的杜氏改良 Eagle 培养基中，于水合胶原凝胶上分别添加或不添加TGF-β1（0、20、40、100、200、400或600 pmol/L）培养1天、2天和3天。
TGF-β1剂量依赖性地增加心脏成纤维细胞介导的胶原凝胶收缩，在100 pmol/L TGF-β1时达到最大效应。TGF-β1还刺激了胶原凝胶格子中心脏成纤维细胞的3(H)-胸苷掺入和总蛋白含量。TGF-β1剂量依赖性地诱导肌成纤维细胞标志物β-平滑肌肌动蛋白增加。TGF-β1诱导的胶原凝胶面积减少与TGF-β1引起的胶原凝胶基质中α-平滑肌肌动蛋白的出现呈负相关。
我们的数据表明，TGF-β1增加了成年大鼠心脏成纤维细胞的收缩活性及其向肌成纤维细胞分化的能力。由于收缩活性与分化相关，TGF-β1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对肌成纤维细胞分化的促进作用。
