The chemokine receptor CCR1 is strongly up-regulated after skin injury but dispensable for wound healing.
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.
Kaesler
Susanne
S
Institute of Cell Biology, Department of Biology, ETH Zürich, Zurich, Switzerland.
Bugnon
Philippe
P
Gao
Ji-Liang
JL
Murphy
Philip M
PM
Goppelt
Andreas
A
Werner
Sabine
S
D000818:Animals; D016207:Cytokines / Q000378:metabolism; D018076:DNA, Complementary / Q000235:genetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D054389:Receptors, CCR1; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism*; D012260:Ribonucleases / Q000378:metabolism; D012867:Skin / Q000293:injuries* / Q000378:metabolism / Q000473:pathology; D015854:Up-Regulation / Q000502:physiology; D014945:Wound Healing / Q000502:physiology*; D014950:Wounds, Penetrating / Q000378:metabolism* / Q000473:pathology
C515301:Ccr1 protein, mouse; D016207:Cytokines; D018076:DNA, Complementary; D054389:Receptors, CCR1; D019707:Receptors, Chemokine; D012260:Ribonucleases