Division of Plastic Surgery, Northwestern University Feinberg School of Medicine, 225 East Chicago Avenue, Chicago, IL, 60611, USA.
Department of Plastic and Reconstructive Surgery, Stanley Manne Children's Research Institute, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, USA.
Sci Rep. 2020 Sep 29;10(1):15991. doi: 10.1038/s41598-020-71823-z.
Tissue expansion procedures (TE) utilize mechanical forces to induce skin growth and regeneration. While the impact of quick mechanical stimulation on molecular changes in cells has been studied extensively, there is a clear gap in knowledge about sequential biological processes activated during long-term stimulation of skin in vivo. Here, we present the first genome-wide study of transcriptional changes in skin during TE, starting from 1 h to 7 days of expansion. Our results indicate that mechanical forces from a tissue expander induce broad molecular changes in gene expression, and that these changes are time-dependent. We revealed hierarchical changes in skin cell biology, including activation of an immune response, a switch in cell metabolism and processes related to muscle contraction and cytoskeleton organization. In addition to known mechanoresponsive genes (TNC, MMPs), we have identified novel candidate genes (SFRP2, SPP1, CCR1, C2, MSR1, C4A, PLA2G2F, HBB), which might play crucial roles in stretched-induced skin growth. Understanding which biological processes are affected by mechanical forces in TE is important for the development of skin treatments to maximize the efficacy and minimize the risk of complications during expansion procedures.
组织扩张术（TE）利用机械力诱导皮肤生长和再生。虽然快速机械刺激对细胞内分子变化的影响已经得到了广泛研究，但对于体内皮肤长期刺激过程中激活的连续生物学过程，我们的认识显然存在空白。在这里，我们首次进行了组织扩张过程中皮肤转录变化的全基因组研究，从扩张的 1 小时到 7 天。我们的结果表明，组织扩张器的机械力会引起基因表达的广泛分子变化，并且这些变化是时间依赖性的。我们揭示了皮肤细胞生物学的层次变化，包括免疫反应的激活、细胞代谢的转变以及与肌肉收缩和细胞骨架组织相关的过程。除了已知的机械响应基因（TNC、MMPs）外，我们还鉴定了新的候选基因（SFRP2、SPP1、CCR1、C2、MSR1、C4A、PLA2G2F、HBB），它们可能在拉伸诱导的皮肤生长中发挥关键作用。了解组织扩张术中机械力影响哪些生物学过程对于开发皮肤治疗方法以最大程度地提高疗效并最小化扩张过程中的并发症风险非常重要。
