title: Cell surface engineering using glycosylphosphatidylinositol anchored tissue inhibitor of matrix metalloproteinase-1 stimulates cutaneous wound healing.
abstract: The balance between matrix metalloproteinases and their endogenous tissue inhibitors (TIMPs) is an important component in effective wound healing. The biologic action of these proteins is linked in part to the stoichiometry of TIMP/matrix metalloproteinases/surface protein interactions. We recently described the effect of a glycosylphosphatidylinositol (GPI) anchored version of TIMP-1 on dermal fibroblast biology. Here, cell proliferation assays, in vitro wound healing, electrical wound, and impedance measurements were used to characterize effects of TIMP-1-GPI treatment on primary human epidermal keratinocytes. TIMP-1-GPI stimulated keratinocyte proliferation, as well as mobilization and migration. In parallel, it suppressed the migration and matrix secretion of dermal myofibroblasts, and reduced their secretion of active TGF-β1. Topical application of TIMP-1-GPI in an in vivo excisional wound model increased the rate of wound healing. The agent positively influenced different aspects of wound healing depending on the cell type studied. TIMP-1-GPI counters potential negative effects of overactive myofibroblasts and enhances the mobilization and proliferation of keratinocytes essential for effective wound healing. The application of TIMP-1-GPI represents a novel and practical clinical solution for facilitating healing of difficult wounds.
authors.affiliation: Medical Clinic and Outpatient Clinic IV, University of Munich, Munich, Germany.
authors.forename: Roghieh
authors.initials: R
authors.lastname: Djafarzadeh
authors.forename: Claudius
authors.initials: C
authors.lastname: Conrad
authors.forename: Susan
authors.initials: S
authors.lastname: Notohamiprodjo
authors.forename: Stephanie
authors.initials: S
authors.lastname: Hipp
authors.forename: Hanno
authors.initials: H
authors.lastname: Niess
authors.forename: Christiane J
authors.initials: CJ
authors.lastname: Bruns
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Nelson
mesh_terms: D015153:Blotting, Western; D002058:Burns, Electric / Q000378:metabolism / Q000473:pathology*; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D005786:Gene Expression Regulation; D017261:Glycosylphosphatidylinositols / Q000378:metabolism*; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism*; D008297:Male; D011956:Receptors, Cell Surface / Q000378:metabolism; D023822:Tissue Engineering; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014945:Wound Healing
chemical_list: D017261:Glycosylphosphatidylinositols; D011956:Receptors, Cell Surface; C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D053773:Transforming Growth Factor beta1