Fibroblasts in mechanically stressed collagen lattices assume a "synthetic" phenotype
Fibroblasts in mechanically stressed collagen lattices assume a "synthetic" phenotype
复制标题
DOI：
10.1074/jbc.m101602200
复制
发表时间：
2001-09-28
影响因子：
4.8
通讯作者：
Eckes, B
中科院分区：
文献类型：
--
作者：
Kessler, D;Dethlefsen, S;Eckes, B
成纤维细胞在创伤愈合、增生性瘢痕形成和纤维化形成等生理和病理状态下，都会受到机械力平衡的影响。然而，成纤维细胞在机械刺激下的分子反应和基因表达的变化仍然知之甚少。作为体外培养模型，人真皮成纤维细胞在高(应力)和低(松弛)张力下，在三维胶原纤维网络中培养。基因芯片技术与Northern印迹分析相结合，鉴定了编码细胞外基质蛋白、纤维化生长因子、蛋白酶抑制物、焦点粘连成分和细胞骨架的机械反应基因。将双轴应变应用于培养在柔性硅胶膜上的成纤维细胞，结果表明，菌株的类型以及底物的性质导致了不同的基因调控模式。胶原蛋白晶格中机械诱导基因的转录图谱表明，机械刺激导致了一种以诱导结缔组织合成为特征，同时抑制基质降解的“合成”成纤维细胞表型。
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.