Abstract：
How reparative processes are coordinated following injury is incompletely understood. In recent studies, we showed that autocrine C3a and C5a receptor (C3ar1 and C5ar1) G protein-coupled receptor signaling plays an obligate role in vascular endothelial growth factor receptor 2 growth signaling in vascular endothelial cells. We documented the same interconnection for platelet-derived growth factor receptor growth signaling in smooth muscle cells, epidermal growth factor receptor growth signaling in epidermal cells, and fibroblast growth factor receptor signaling in fibroblasts, indicative of a generalized cell growth regulatory mechanism. In this study, we examined one physiological consequence of this signaling circuit. We found that disabling CD55 (also known as decay accelerating factor), which lifts restraint on autocrine C3ar1/C5ar1 signaling, concomitantly augments the growth of each cell type. The mechanism is heightened C3ar1/C5ar1 signaling resulting from the loss of CD55\'s restraint jointly potentiating growth factor production by each cell type. Examination of the effect of lifted CD55 restraint in four types of injury (burn, corneal denudation, ear lobe puncture, and reengraftment of autologous skin) showed that disabled CD55 function robustly accelerated healing in all cases, whereas disabled C3ar1/C5ar1 signaling universally retarded it. In wild-type mice with burns or injured corneas, applying a mouse anti-mouse CD55 blocking Ab (against CD55\'s active site) to wounds accelerated the healing rate by 40-70%. To our knowledge, these results provide new insights into mechanisms that underlie wound repair and open up a new tool for accelerating healing.
摘要：
损伤后如何协调修复过程尚不完全清楚。在最近的研究中,我们发现自分泌C3a和C5a受体(C3ar1和C5ar1)G蛋白偶联受体信号在血管内皮细胞的血管内皮生长因子受体2生长信号中起着专性作用.我们记录了平滑肌细胞中血小板衍生生长因子受体生长信号的相同相互联系，表皮细胞中的表皮生长因子受体生长信号，和成纤维细胞生长因子受体信号传导，表明了广泛的细胞生长调节机制。在这项研究中,我们检查了这个信号回路的一个生理后果。我们发现禁用CD55(也称为衰减加速因子)，解除对自分泌C3ar1/C5ar1信号的约束，同时增强每种细胞类型的生长。其机制是C3ar1/C5ar1信号传导增强，这是由于CD55的抑制作用丧失共同增强了每种细胞类型的生长因子产生。检查解除CD55约束在四种类型的损伤中的作用（烧伤，角膜剥脱,耳垂穿刺,和自体皮肤的重新植入）表明，在所有情况下，残疾的CD55功能都强劲地加速了愈合，而禁用C3ar1/C5ar1信号普遍阻碍了它。在烧伤或角膜损伤的野生型小鼠中，将小鼠抗小鼠CD55阻断Ab（针对CD55的活性位点）应用于伤口可将愈合率加速40-70％。据我们所知,这些结果为伤口修复的基础机制提供了新的见解，并为加速愈合开辟了新的工具。
