Role of scaffold stiffness dependent durotaxis on development of keloid

瘢痕疙瘩是一种皮肤纤维性疾病，可由皮肤上的轻微侮辱引起，如粉刺或耳洞，或严重损伤，如烧伤。瘢痕疙瘩以胶原等细胞外基质过度沉积为特征，其组织学形态具有一定的特点。瘢痕疙瘩多发生在胸部、肩部或肘关节等部位，易受机械牵拉的影响。因此，我们认为瘢痕疙瘩成纤维细胞对机械应力的反应可能与正常皮肤成纤维细胞不同。我们使用细胞拉伸仪(NC-500)分析了其对机械应力的敏感性，该设备上有培养成纤维细胞的硅室。我们利用基因芯片阵列研究了周期性细胞伸展对差异基因表达的影响。我们发现，与正常皮肤成纤维细胞相比，瘢痕疙瘩成纤维细胞编码细胞骨架、膜蛋白和细胞因子的某些基因发生了强烈的变化(我们在日本整形和重建外科学会第14届研究理事会会议上报道)。此外，我们还通过一组抗体发现，在瘢痕疙瘩成纤维细胞中，rac1蛋白的表达高于正常皮肤成纤维细胞。此外，我们还分析了细胞拉伸后细胞内分子的表达变化。我们将成纤维细胞培养在硬度可变的弹性胶原包被的聚丙烯酰胺凝胶上，发现细胞的形状和增殖率取决于聚丙烯酰胺凝胶的硬度。

Keloids are skin fibrotic conditions that can be caused by minor insults to skin, such as acne or ear piercing, or by severe injuries such as burns. Keloids are characterized by an overabundant deposition of extra-cellular matrix such as collagen, and their histologic morphology has a characteristic manner. Keloid occurs more often on chest, shoulder or elbow-joint etc. which is easily affected by mechanical stretch. So we consider that the response to mechanical stress of fibroblast derived from Keloid may be different from that of normal skin fibroblast. We analyzed the sensitivity to mechanical stress using cell stretch apparatus (NC-500) which has silicon chambers on which the fibroblasts are cultured. We investigated differential gene expression in response to cyclic cell stretching by gene chip array. We found that some genes of keloid fibroblasts encoding cellular skeleton, membrane proteins and cytokines were strongly changed compared to normal skin fibroblasts (We reported at The 14^<th> Research Council Meeting of Japan Society of Plastic and Reconstructive Surgery). Furthermore we found that the expression of rac1 protein is higher in keloid fibroblasts than in normal skin fibroblasts by panel of antibodies. In addition, we analyzed expression change of intracellular molecules after cell stretching. We cultured fibroblasts on elastic collagen coated polyacrylamide gel whose hardness is changeable and we found that cell shape and proliferation rate are variable depending on hardness of polyacrylamide gel.