Kessler D, Dethlefsen S, Haase I, Plomann M, Hirche F, Krieg T, Eckes B
Department of Dermatology, Joseph-Stelzmann Strasse 9, University of Cologne, 50931 Köln, Germany.
J Biol Chem. 2001 Sep 28;276(39):36575-85. doi: 10.1074/jbc.M101602200. Epub 2001 Jul 23.
Fibroblasts are subjected to changes of the mechanical force balance during physiological as well as pathological situations, such as wound healing, development of hypertrophic scars, and fibrogenesis. However, the molecular response and the changes in fibroblast gene expression upon mechanical stimulation remain poorly understood. As an in vitro model, human dermal fibroblasts were cultured within a three-dimensional network of fibrillar collagen either under high (stressed) or low tension (relaxed). cDNA microarray technology in combination with Northern blot analysis led to identification of mechano-responsive genes coding for extracellular matrix proteins, fibrogenic growth factors, protease inhibitors, components of focal adhesions, and the cytoskeleton. Application of biaxial strain to fibroblasts cultured on flexible silicone membranes revealed that the type of strain as well as the properties of the substrate induced different patterns of gene regulation. The transcriptional profile of mechanically induced genes in collagen lattices suggests that mechanical stimuli lead to a "synthetic" fibroblast phenotype characterized by induction of connective tissue synthesis while simultaneously inhibiting matrix degradation.
在生理和病理情况下，如伤口愈合、肥厚性瘢痕形成和纤维化过程中，成纤维细胞会受到机械力平衡的变化影响。然而，机械刺激后成纤维细胞的分子反应以及基因表达变化仍知之甚少。作为体外模型，人皮肤成纤维细胞在高张力（应激）或低张力（松弛）条件下，培养于三维纤维状胶原网络中。cDNA微阵列技术结合Northern印迹分析，鉴定出了编码细胞外基质蛋白、促纤维化生长因子、蛋白酶抑制剂、黏着斑成分和细胞骨架的机械反应基因。对培养在柔性硅膜上的成纤维细胞施加双轴应变，结果表明应变类型以及底物特性会诱导不同的基因调控模式。胶原晶格中机械诱导基因的转录谱表明，机械刺激会导致成纤维细胞呈现“合成”表型，其特征为诱导结缔组织合成，同时抑制基质降解。
