Identification of a myofibroblast-specific expression signature in skin wounds
Identification of a myofibroblast-specific expression signature in skin wounds
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DOI：
10.1016/j.matbio.2017.07.005
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发表时间：
2018-01-01
期刊：
影响因子：
6.9
通讯作者：
Brachvogel, Bent
中科院分区：
文献类型：
--
作者：
Bergmeier, Vera;Etich, Julia;Brachvogel, Bent
在皮肤损伤后，成纤维细胞迁移到伤口中并转化为可收缩的、产生细胞外基质的肌成纤维细胞以促进皮肤修复。肌成纤维细胞的持续激活可引起过度的纤维化反应，但其潜在机制尚未完全了解。我们使用SMA-GFP转基因小鼠来研究皮肤伤口中肌成纤维细胞的募集和活化。肌成纤维细胞最初在损伤后三天被招募到伤口，它们的数量在七天后达到最大值，随后下降。表达谱分析显示，1749个基因在损伤后7天的伤口中分选的肌成纤维细胞中差异表达。这些基因中的大多数与细胞外区和细胞外周相连，包括编码细胞外基质蛋白的基因。一组独特的核心基质体和基质体相关基因在肌成纤维细胞中差异表达，并发现了几个尚不知道与肌成纤维细胞介导的伤口愈合相关的基因（例如Co 124 a1、Podnl 1、Bvcan、Tinag 11、Thbs 3、Adamts 16、Adamts 19、Cxcl's、Ccl's）。此外，一个复杂的网络G蛋白偶联的信号转导事件的调节肌成纤维细胞（如Adcyl，Plbc 4，Gnas）。因此，在原位肉芽组织形成的峰值处的成肌纤维细胞特异性表达谱的这一首次表征为可能在纤维化反应期间控制过度ECM沉积的新型靶基因提供了重要的见解。(C)2017爱思唯尔B. V.保留所有权利。
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. Co124a1, Podnl1, Bvcan, Tinag11, 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. (C) 2017 Elsevier B.V. All rights reserved.