Mutations in collagen V are associated with classic Ehlers-Danlos syndrome (EDS). A significant percentage of these mutations result in haploinsufficiency for collagen V. The purpose of this work was to determine if changes in collagen V expression are associated with altered dermal fibroblast behavior contributing to the poor wound healing response. A haploinsufficient Col5a1+/- mouse model of EDS was utilized. In vivo wound healing studies demonstrated that mutant mice healed significantly slower than Col5a1+/+ mice. The basis for this difference was examined in vitro using dermal fibroblast strains isolated from Col5a1+/- and Col5a1+/+ mice. Fibroblast proliferation was determined for each strain by counting cells at different time points after seeding as well as using the proliferation marker Ki-67. Fibroblastattachment to collagens I, III, and fibronectin also was analyzed. In addition, in vitro scratch wounds were used to analyze fibroblast wound closure. Significantly decreased fibroblast proliferation was observed in Col5a1+/- compared to Col5a1+/+ fibroblasts. Our data indicate that the decreased fibroblast number was not due to apoptosis. Wild type Col5a1+/+ fibroblasts attached significantly better to components of the wound matrix (collagens I, III and fibronectin) than Col5a1+/- fibroblasts. A significant difference in in vitro scratch wound closure rates also was observed. Col5a1+/+ fibroblasts closed wounds in 22hr while Col5a1+/- fibroblasts demonstrated ∼80% closure. There were significant differences in closure at all time points analyzed. Our data suggest that decreased fibroblast proliferation, extracellular matrix attachment, and migration contribute to the decreased wound healing response in classic EDS.
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