title: Matrix metalloproteinase activity and immunohistochemical profile of matrix metalloproteinase-2 and -9 and tissue inhibitor of metalloproteinase-1 during human dermal wound healing.
abstract: Proteolytic activity is required for the turnover of the extracellular matrix during wound healing. Matrix metalloproteinases can collectively cleave all components of the extracellular matrix, with the endogenous tissue inhibitor of metalloproteinase-1 regulating their activity. Breast tissue taken at varying postoperative times (n= 92) or during surgery (controls, n= 17), was used to investigate the temporal and spatial activity of matrix metalloproteinase-2 and -9 and tissue inhibitor of metalloproteinase-1 during human wound healing. Matrix metalloproteinase activity, determined using a quenched fluorescence substrate assay, increased during early healing (3-8 weeks) compared to controls, and then decreased between 24 and 36 weeks after surgery (p < 0.05 until 24 weeks, Mann-Whitney U-test). Immunohistochemistry scores for matrix metalloproteinase-9 expression were significantly elevated compared to controls in scar endothelial cells and fibroblasts from 2 until 12 and 20 weeks, respectively. Matrix metalloproteinase-2 staining was observed exclusively in fibroblasts, reaching maximum levels 8-12 weeks after surgery, decreasing by 1.5 years but remaining significantly increased. Tissue inhibitor of metalloproteinase-1 staining was relatively sparse but was significantly increased until 8 weeks after surgery. These results show that matrix metalloproteinases are present at elevated levels during early wound healing, when angiogenesis occurs, and suggest that matrix metalloproteinase-9 may play a significant role. The later expression of matrix metalloproteinase-2 and -9 in fibroblasts suggests a role in extracellular matrix remodeling.
authors.affiliation: Academic Unit of Surgical Oncology, School of Medicine and Biomedical Sciences, University of Sheffield, Royal Hallamshire Hospital, Sheffield S10 2JF, United Kingdom.
authors.forename: Judith A
authors.initials: JA
authors.lastname: Gillard
authors.forename: Malcolm W R
authors.initials: MW
authors.lastname: Reed
authors.forename: David
authors.initials: D
authors.lastname: Buttle
authors.forename: Simon S
authors.initials: SS
authors.lastname: Cross
authors.forename: Nicola J
authors.initials: NJ
authors.lastname: Brown
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D001940:Breast / Q000473:pathology*; D001943:Breast Neoplasms / Q000473:pathology / Q000601:surgery; D002921:Cicatrix / Q000473:pathology / Q000503:physiopathology; D020405:Dermis / Q000473:pathology / Q000502:physiology; D005109:Extracellular Matrix / Q000473:pathology / Q000502:physiology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008408:Mastectomy; D020778:Matrix Metalloproteinase 2 / Q000502:physiology*; D020780:Matrix Metalloproteinase 9 / Q000502:physiology*; D008875:Middle Aged; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000502:physiology*; D014945:Wound Healing / Q000502:physiology*
chemical_list: D019715:Tissue Inhibitor of Metalloproteinase-1; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9