Moulin V, Castilloux G, Auger F A, Garrel D, O'Connor-McCourt M D, Germain L
Laboratoire de recherche des grands brûlés/LOEX, Hôpital du Saint-Sacrement, Québec, Canada.
Exp Cell Res. 1998 Jan 10;238(1):283-93. doi: 10.1006/excr.1997.3827.
Myofibroblasts play an important role in normal wound healing. They are present transiently during tissue repair. Their differentiation from fibroblasts and their role in granulation tissues are most likely to be modulated by cytokines. As these cells are derived from normal fibroblasts, their responses to cytokines are assumed to be similar. Until now, however, the difficulties in obtaining and maintaining normal human wound healing myofibroblasts in vitro have hampered comparison. The present study was designed to determine the effect of TGF-beta 1 and IFN-gamma, two cytokines known to modulate fibroblast morphology, on wound healing myofibroblasts and to compare it to fibroblasts. Morphological and phenotypic changes were followed by light and electron microscopy (stress fibers) and immunofluorescence cytochemistry (alpha-SM actin). Functional parameters such as the capacity to synthesize collagen and collagen gel contraction were studied. Both cytokines induced a strong modification of growth rate and phenotypic and morphological parameters in fibroblasts whereas collagen synthesis was slightly changed. Furthermore, TGF-beta 1 increased contractile capacity of fibroblasts whereas IFN-gamma greatly decreased it. In myofibroblasts, TGF-beta 1 and IFN-gamma did not induce any variation of morphology or growth rate. Interestingly, a strong modulation of functional parameters was observed: collagen synthesis was highly modified and, as for fibroblasts, the contractile capacity was altered. However, inhibition of contraction by IFN-gamma was irreversible in myofibroblasts but not in fibroblasts. These results suggest that fibroblastic cells show modulated responses to cytokines according to their stage of differentiation during wound healing.
肌成纤维细胞在正常伤口愈合中发挥着重要作用。它们在组织修复过程中短暂存在。它们从成纤维细胞分化而来，并且它们在肉芽组织中的作用很可能受到细胞因子的调节。由于这些细胞源自正常成纤维细胞，因此假定它们对细胞因子的反应相似。然而，到目前为止，在体外获取和维持正常人伤口愈合肌成纤维细胞的困难阻碍了比较研究。本研究旨在确定已知可调节成纤维细胞形态的两种细胞因子——转化生长因子β1（TGF-β1）和γ干扰素（IFN-γ）对伤口愈合肌成纤维细胞的影响，并将其与成纤维细胞进行比较。通过光学显微镜和电子显微镜（观察应力纤维）以及免疫荧光细胞化学（检测α-平滑肌肌动蛋白）来跟踪形态和表型变化。研究了诸如合成胶原蛋白的能力和胶原蛋白凝胶收缩等功能参数。两种细胞因子均诱导成纤维细胞的生长速率、表型和形态参数发生强烈改变，而胶原蛋白合成略有变化。此外，TGF-β1增加了成纤维细胞的收缩能力，而IFN-γ则大大降低了其收缩能力。在肌成纤维细胞中，TGF-β1和IFN-γ未诱导形态或生长速率的任何变化。有趣的是，观察到功能参数有强烈调节：胶原蛋白合成被高度改变，并且与成纤维细胞一样，收缩能力也发生了改变。然而，IFN-γ对肌成纤维细胞收缩的抑制是不可逆的，而成纤维细胞则不然。这些结果表明，成纤维细胞样细胞根据其在伤口愈合过程中的分化阶段对细胞因子表现出不同的反应。
