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Cell surface engineering using glycosylphosphatidylinositol anchored tissue inhibitor of matrix metalloproteinase‐1 stimulates cutaneous wound healing
Author(s) -
Djafarzadeh Roghieh,
Conrad Claudius,
Notohamiprodjo Susan,
Hipp Stephanie,
Niess Hanno,
Bruns Christiane J.,
Nelson Peter J.
Publication year - 2014
Publication title -
wound repair and regeneration
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.847
H-Index - 109
eISSN - 1524-475X
pISSN - 1067-1927
DOI - 10.1111/wrr.12132
Subject(s) - wound healing , matrix metalloproteinase , keratinocyte , fibroblast , microbiology and biotechnology , secretion , chemistry , extracellular matrix , myofibroblast , cell migration , matrix (chemical analysis) , in vivo , in vitro , cancer research , immunology , medicine , biology , pathology , biochemistry , fibrosis , chromatography
Abstract The balance between matrix metalloproteinases and their endogenous tissue inhibitors ( TIMP s) 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 T GF ‐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.