HGFA Is an Injury-Regulated Systemic Factor that Induces the Transition of Stem Cells into GAlert
HGFA Is an Injury-Regulated Systemic Factor that Induces the Transition of Stem Cells into GAlert
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DOI：
10.1016/j.celrep.2017.03.066
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发表时间：
2017-04-18
期刊：
影响因子：
8.8
通讯作者：
Rando, Thomas A.
中科院分区：
文献类型：
--
作者：
Rodgers, Joseph T.;Schroeder, Matthew D.;Rando, Thomas A.
激活静止干细胞进入细胞周期是启动组织修复过程的关键步骤。我们最近报道了静止干细胞可以转变为G（警报），在这种细胞状态下，它们具有增强的激活和参与组织修复的功能能力。然而，在干细胞中诱导G（Alert）的精确分子信号仍然是难以捉摸的。在这里，我们发现损伤诱导的肝细胞生长因子（HGF）蛋白水解过程通过系统性蛋白酶，肝细胞生长因子激活剂（HGFA），刺激骨骼肌干细胞（MuSCs）和纤维脂肪源性祖细胞（FAPs）中的G（Alert）。我们证明，给动物注射活性HGFA足以诱导全身干细胞中的G(Alert)，并显著加速干细胞激活和组织修复的过程。我们的数据表明，诱导G（Alert）的因子将在再生医学和伤口愈合方面具有广泛的治疗应用。
The activation of quiescent stem cells into the cell cycle is a key step in initiating the process of tissue repair. We recently reported that quiescent stem cells can transition into G(Alert), a cellular state in which they have an increased functional ability to activate and participate in tissue repair. However, the precise molecular signals that induce G(Alert) in stem cells have remained elusive. Here, we show that the injury-induced regulation of hepatocyte growth factor (HGF) proteolytic processing via the systemic protease, hepatocyte growth factor activator (HGFA), stimulates G(Alert) in skeletal muscle stem cells (MuSCs) and fibro-adipogenic progenitors (FAPs). We demonstrate that administering active HGFA to animals is sufficient to induce G(Alert) in stem cells throughout the body and to significantly accelerate the processes of stem cell activation and tissue repair. Our data suggest that factors that induce G(Alert) will have broad therapeutic applications for regenerative medicine and wound healing.