title: Impaired wound contraction in stromelysin-1-deficient mice.
abstract: OBJECTIVE
  To determine whether the deletion of stromelysin-1, a single metalloproteinase gene product, will alter the time course and quality of dermal wound repair in mice.
  
  
  BACKGROUND
  After dermal injury, a highly coordinated program of events is initiated by formation of a fibrin clot, followed by migration of keratinocytes, contraction of the dermis, recruitment of inflammatory macrophages, formation of granulation tissue with angiogenesis, and finally tissue remodeling. Matrix metalloproteinases are rapidly induced in the dermis and granulation tissue and at the leading edge of the epidermis in the healing wounds.
  
  
  METHODS
  Incisional and circular full-thickness wounds 2 to 10 mm were made in the dermis of stromelysin-1-deficient and wild-type mice. The wounds were analyzed for rate of cellular migration and epithelialization. The wound contraction was examined by immunohistochemical staining for alpha-smooth muscle actin and fluorescent staining for fibrillar actin.
  
  
  RESULTS
  Independent of the age of the animal, excisional wounds in stromelysin-1-deficient mice failed to contract and healed more slowly than those in wild-type mice. Cellular migration and epithelialization were unaffected in the stromelysin-1-deficient animals. The functional defect in these mice is failure of contraction during the first phase of healing because of inadequate organization of actin-rich stromal fibroblasts.
  
  
  CONCLUSIONS
  Excisional dermal wound healing is impaired in mice with a targeted deletion in the stromelysin-1 gene. Incisional wound healing is not affected. These data implicate stromelysin-1 proteolysis during early wound contraction and indicate that stromelysin-1 is crucial for the organization of a multicellular actin network.
authors.affiliation: Department of Surgery, University of California, San Francisco 94143-0570, USA.
authors.forename: K M
authors.initials: KM
authors.lastname: Bullard
authors.forename: L
authors.initials: L
authors.lastname: Lund
authors.forename: J S
authors.initials: JS
authors.lastname: Mudgett
authors.forename: T N
authors.initials: TN
authors.lastname: Mellin
authors.forename: T K
authors.initials: TK
authors.lastname: Hunt
authors.forename: B
authors.initials: B
authors.lastname: Murphy
authors.forename: J
authors.initials: J
authors.lastname: Ronan
authors.forename: Z
authors.initials: Z
authors.lastname: Werb
authors.forename: M J
authors.initials: MJ
authors.lastname: Banda
mesh_terms: D000818:Animals; D019278:Matrix Metalloproteinase 3 / Q000172:deficiency* / Q000235:genetics; D051379:Mice; D009154:Mutation; D014945:Wound Healing / Q000235:genetics
chemical_list: D019278:Matrix Metalloproteinase 3