After skin injury fibroblasts migrate into the wound and transform into contractile, extracellular matrix-producing myofibroblasts to promote skin repair. Persistent activation of myofibroblasts can cause excessive fibrotic reactions, but the underlying mechanisms are not fully understood. We used SMA-GFP transgenic mice to study myofibroblast recruitment and activation in skin wounds. Myofibroblasts were initially recruited to wounds three days post injury, their number reached a maximum after seven days and subsequently declined. Expression profiling showed that 1749 genes were differentially expressed in sorted myofibroblasts from wounds seven days post injury. Most of these genes were linked with the extracellular region and cell periphery including genes encoding for extracellular matrix proteins. A unique panel of core matrisome and matrisome-associated genes was differentially expressed in myofibroblasts and several genes not yet known to be linked to myofibroblast-mediated wound healing were found (e.g. Col24a1, Podnl1, Bvcan, Tinagl1, Thbs3, Adamts16, Adamts19, Cxcl's, Ccl's). In addition, a complex network of G protein-coupled signaling events was regulated in myofibroblasts (e.g. Adcy1, Plbc4, Gnas). Hence, this first characterization of a myofibroblast-specific expression profile at the peak of in situ granulation tissue formation provides important insights into novel target genes that may control excessive ECM deposition during fibrotic reactions.

中文翻译：

---

皮肤伤口中成肌纤维细胞特异性表达特征的鉴定。

皮肤损伤后，成纤维细胞迁移到伤口中，并转变为可收缩的，产生细胞外基质的成肌纤维细胞，从而促进皮肤修复。肌成纤维细胞的持续激活会引起过度的纤维化反应，但其潜在机制尚不完全清楚。我们使用SMA-GFP转基因小鼠研究了肌成纤维细胞在皮肤伤口中的募集和活化。肌成纤维细胞最初在受伤后三天被招募到伤口，七天后达到了最大值，随后下降。表达谱分析显示，受伤后7天，来自分类的成肌纤维细胞中有1749个基因差异表达。这些基因大多数与细胞外区域和细胞外围相关，包括编码细胞外基质蛋白的基因。在成肌纤维细胞中差异表达了一组独特的核心母体和与母体相关的基因，发现了一些未知的与肌纤维母细胞介导的伤口愈合相关的基因（例如Col24a1，Podnl1，Bvcan，Tinagl1，Thbs3，Adamts16，Adamts19，Cxcl's ，Ccl）。此外，在成肌纤维细胞（例如，Adcy1，Plbc4，Gnas）中，G蛋白偶联的信号事件的复杂网络受到调节。因此，肌成纤维细胞特异性表达谱在原位肉芽组织形成高峰期的首次表征为重要的洞察力提供了新的靶基因的见解，该靶基因可控制纤维化反应期间过多的ECM沉积。Podnl1，Bvcan，Tinagl1，Thbs3，Adamts16，Adamts19，Cxcl，Ccl）。此外，在成肌纤维细胞（例如，Adcy1，Plbc4，Gnas）中，G蛋白偶联的信号事件的复杂网络受到调节。因此，肌成纤维细胞特异性表达谱在原位肉芽组织形成高峰期的首次表征为重要的洞察力提供了新的靶基因的见解，该靶基因可控制纤维化反应期间过多的ECM沉积。Podnl1，Bvcan，Tinagl1，Thbs3，Adamts16，Adamts19，Cxcl，Ccl）。此外，在成肌纤维细胞（例如，Adcy1，Plbc4，Gnas）中，G蛋白偶联的信号事件的复杂网络受到调节。因此，肌成纤维细胞特异性表达谱在原位肉芽组织形成高峰期的首次表征为重要的洞察力提供了新的靶基因的见解，该靶基因可控制纤维化反应期间过多的ECM沉积。