Severely impaired wound healing in the collagenase-resistant mouse.
Collagen in the skin undergoes dramatic reorganization during wound repair. Matrix metalloproteinases degrade and remodel the collagen in a tightly controlled process. The collagenase-resistant mouse, Col1a1(tm1Jae), has been developed to produce collagen type I, which is resistant to degradation by human matrix metalloproteinase 1. These mice grow normally but develop thickened skin with age. We investigated the effect of this mutant collagen on wound repair. Incisional wounds were made on Col1a1(tm1Jae) homozygous mutant (Col1a1(r/r)) and wild-type (Col1a1+/+) mice and these wounds were harvested at 1 and 6 h, 1, 2, 3, 7, 10, 14, and 70 d post wounding. Wound healing was severely delayed in Col1a1(r/r) wounds, with wounds remaining significantly wider than wild-type for the first 2 wk after injury. Reepithelialization of the Col1a1(r/r) wounds took 7 d longer than in the wild-type. The Col1a1(r/r) wounds had a prolonged early inflammatory response. Immunostaining for matrix metalloproteinases revealed significant upregulation of matrix metalloproteinase 13 in Col1a1(r/r) wounds, but minimal changes in other matrix metalloproteinases. There was no significant difference in scarring between Col1a1(r/r) and Col1a1+/+ wounds after 70 d.
Beare
Alice H M
AH
Division of Immunology, Microbiology and Development, and UK Centre for Tissue Engineering, School of Biological Sciences, University of Manchester, UK.
O'Kane
Sharon
S
Krane
Stephen M
SM
Ferguson
Mark W J
MW
D000199:Actins / Q000032:analysis; D000818:Animals; D017364:Collagenases / Q000032:analysis / Q000502:physiology*; D007249:Inflammation / Q000473:pathology; D053509:Matrix Metalloproteinase 13; D008666:Metalloendopeptidases / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D014945:Wound Healing / Q000502:physiology*; D014947:Wounds and Injuries / Q000473:pathology
D000199:Actins; D018809:Proliferating Cell Nuclear Antigen; D017364:Collagenases; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13; D008666:Metalloendopeptidases; C507081:Mmp13 protein, mouse