Kuang Ruixia, Wang Zhiguo, Xu Quanchen, Cai Xia, Liu Tao
From the *Department of Plastic and Aesthetic Surgery, †Department of Stomatology, and ‡Department of Pharmacy, the Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.
Ann Plast Surg. 2016 Apr;76(4):388-93. doi: 10.1097/SAP.0000000000000654.
Mechanical strain is a key contributor in the pathogenesis of hypertrophic scarring, whose optimal stretch magnitudes to initiate the differentiation of normal skin fibroblasts into aberrant fibroblasts phenotype remains largely unresolved. Influence of varying cyclic strain magnitudes on cultured human normal skin fibroblasts and its transformation into hypertrophic scar fibroblast-like phenotype is investigated in this study. Cultured fibroblasts isolated from hypertrophic scar and normal skin tissue were subjected to cyclic mechanical stretching under individual 10%, 15%, and 20% strain magnitudes at a frequency of 0.1 Hz for 24 hours. Stretched normal skin fibroblasts demonstrated significantly increased rates of cell proliferation, and also apparently oriented away nearly perpendicular to the applied stretching direction. Interestingly, the applied 10% strains magnitude resulted in a markedly enhanced cell proliferative ability compared with that of 20% strain magnitude. Parameters involving the mechanotransduction signaling, such as integrin β1 and P130Cas, were significantly improved at both mRNA and protein levels in the stretched normal skin fibroblasts, which was demonstrated in a negative magnitude-dependent manner. In addition, 10% strains magnitude triggered the highest expression levels of growth factor TGF-β1 and collagen matrix in stretched normal skin fibroblasts. Collectively, these results indicate that the 10% stretching magnitude, of the 3 strain magnitudes studied, is most effective for triggering the optimal mechanotransduction effects and biological responses inside cultured skin fibroblasts. The demonstrable conversion of normal skin fibroblasts into hypertrophic scar fibroblasts was also observed when 10% stretching magnitude was applied to cultured fibroblasts in vitro.
机械应变是肥厚性瘢痕发病机制中的一个关键因素，然而，启动正常皮肤成纤维细胞分化为异常成纤维细胞表型的最佳拉伸幅度在很大程度上仍未得到解决。本研究探讨了不同循环应变幅度对培养的人正常皮肤成纤维细胞的影响及其向肥厚性瘢痕成纤维细胞样表型的转化。从肥厚性瘢痕和正常皮肤组织中分离培养的成纤维细胞，在频率为0.1Hz的情况下，分别在10%、15%和20%的应变幅度下进行循环机械拉伸24小时。拉伸后的正常皮肤成纤维细胞显示出细胞增殖率显著增加，并且明显几乎垂直于施加的拉伸方向排列。有趣的是，与20%应变幅度相比，施加10%应变幅度导致细胞增殖能力显著增强。涉及机械转导信号的参数，如整合素β1和P130Cas，在拉伸后的正常皮肤成纤维细胞的mRNA和蛋白质水平上均显著改善，且呈负幅度依赖性。此外，10%应变幅度在拉伸后的正常皮肤成纤维细胞中引发了生长因子TGF-β1和胶原基质的最高表达水平。总体而言，这些结果表明，在所研究的3种应变幅度中，10%的拉伸幅度对于触发培养的皮肤成纤维细胞内的最佳机械转导效应和生物学反应最为有效。当在体外对培养的成纤维细胞施加10%的拉伸幅度时，还观察到正常皮肤成纤维细胞明显转化为肥厚性瘢痕成纤维细胞。
