Ira M Herman
Tufts University School of Medicine, USA
Posters & Accepted Abstracts: Eur J Exp Bio
Recently, our work has revealed that clostridial collagenase stimulates extracellular matrix remodeling along with epithelial and vascular cell injury responses while promoting impaired wound healing in vivo. Herein, we will review published findings and preliminary work yet to be published, which demonstrate that bacterial collagenase promotes wound healing responses by elaborating bioactive matrix fragments that stimulate epithelial, fibroblastic and angiogenic responses to injury. To these ends, we performed limited digestions of defined human dermal capillary-derived endothelial (HMVEC) and human fibroblast (HF)-derived extracellular matrices while MS/MS mass spectrometry was used to reveal several collagenase-generated matrix fragments derived from collagen and or collagen-associated proteins. Chemical synthesis and re-combination of some of these bioactive peptides were then used in several cells and animal-based wound healing assays to ascertain whether one or another peptide could activate cellular responses to injury in vitro and impaired wound healing in vivo. Results reveal that several peptides discovered significantly promote cell proliferation and angiogenesis in vitro and stimulate impaired wound healing in vivo. These findings indicate that collagenase indirectly possesses wound healing activity by the creation of bioactive peptides and that these wound healing peptides can convert non-healing wounds into those capable of closure.
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