Variable impairment of wound healing in the heterozygous collagenase-resistant mouse.
Collagen undergoes dramatic reorganization during wound repair. Matrix metalloproteinases degrade and remodel collagen in a tightly controlled process. The collagenase-resistant mouse, Col1a1(tm1Jae), produces type I collagen, which is resistant to degradation by human matrix metalloproteinase 1. These mice grow normally but develop thickened skin with age. We have previously reported that the early wound repair response in homozygous mutant (Col1a1(r/r)) mice is delayed compared to wild type (Col1a1(+/+)). However, the late-stage scar of Col1a1(r/r) wounds was not significantly altered compared to Col1a1(+/+). Here we have investigated the response of heterozygous mice (Col1a1(+/r)) to wounding, not previously reported. Wound reepithelialization was delayed to a similar degree to wounds in the Col1a1(r/r) mice. However, the recovery of impaired wound contraction was faster in Col1a1(+/r) than in Col1a1(r/r) mice, but still slower than in wild-type animals. Analysis of wound protein extracts showed expression of some matrix metalloproteinases was prolonged in both the Col1a1(r/r) and Col1a1(+/r) wounds compared to wild type. We suggest the partial resistance of collagen to collagenase-mediated degradation in the heterozygous animals causes equivalent impairment of keratinocyte migration compared to homozygous collagenase-resistant mice, but that wound contraction during late-stage healing is only partially retarded.
Beare
Alice H M
AH
United Kingdom Center for Tissue Engineering and Division of Immunology, Microbiology, Development and Repair, School of Biological Sciences, University of Manchester, Manchester, United Kingdom.
Krane
Stephen M
SM
Ferguson
Mark W J
MW
D000818:Animals; D003094:Collagen / Q000378:metabolism; D024042:Collagen Type I / Q000378:metabolism*; D000090602:Collagen Type I, alpha 1 Chain; D017364:Collagenases / Q000172:deficiency / Q000502:physiology*; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D023421:Models, Animal; D012867:Skin / Q000293:injuries / Q000503:physiopathology; D012883:Skin Ulcer / Q000503:physiopathology*; D014945:Wound Healing / Q000502:physiology*
D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D003094:Collagen; D017364:Collagenases; D020782:Matrix Metalloproteinases