Kaesler Susanne, Bugnon Philippe, Gao Ji-Liang, Murphy Philip M, Goppelt Andreas, Werner Sabine
Institute of Cell Biology, Department of Biology, ETH Zürich, Zurich, Switzerland.
Wound Repair Regen. 2004 Mar-Apr;12(2):193-204. doi: 10.1111/j.1067-1927.2004.012112.x.
To identify key regulators of cutaneous wound repair, we analyzed a subtractive cDNA library of normal and wounded mouse skin. One of the identified genes encodes the chemokine receptor CCR1, which binds several chemokines present at the wound site. Expression of CCR1 was barely detectable in nonwounded skin, but strong up-regulation was observed after injury to wild-type mice. Most important, the healing abnormalities observed in glucocorticoid-treated mice and activin-overexpressing transgenic mice correlated with an altered expression of CCR1. CCR1-positive cells were identified as macrophages and neutrophils within the wounded area. To determine the importance of CCR1 for wound repair, we analyzed this process in CCR1 knockout mice. Surprisingly, no alterations in either wound closure, wound appearance, wound bursting strength, granulation tissue formation, or re-epithelialization were observed. In addition, the inflammatory response was unaltered in CCR1-deficient mice and the expression of several chemokines, chemokine receptors, and other important regulators of wound repair were normal in these animals. These results show that CCR1 is dispensable for wound healing, most likely due to redundancy in chemokine/chemokine receptor signaling.
为了鉴定皮肤伤口修复的关键调节因子，我们分析了正常和受伤小鼠皮肤的消减cDNA文库。其中一个鉴定出的基因编码趋化因子受体CCR1，它能结合伤口部位存在的几种趋化因子。在未受伤的皮肤中几乎检测不到CCR1的表达，但在野生型小鼠受伤后观察到其强烈上调。最重要的是，在糖皮质激素处理的小鼠和激活素过表达的转基因小鼠中观察到的愈合异常与CCR1表达的改变相关。CCR1阳性细胞被鉴定为伤口区域内的巨噬细胞和中性粒细胞。为了确定CCR1对伤口修复的重要性，我们在CCR1基因敲除小鼠中分析了这一过程。令人惊讶的是，在伤口闭合、伤口外观、伤口破裂强度、肉芽组织形成或重新上皮化方面均未观察到改变。此外，CCR1缺陷小鼠的炎症反应未改变，并且在这些动物中几种趋化因子、趋化因子受体和其他重要伤口修复调节因子的表达均正常。这些结果表明，CCR1对于伤口愈合是可有可无的，很可能是由于趋化因子/趋化因子受体信号传导的冗余性。
