Rescue of Migratory Defects of Ehlers–Danlos Syndrome Fibroblasts In Vitro by Type V Collagen but not Insulin-Like Binding Protein-1

Abstract

Mutations in the genes encoding for type V collagen have been found in the classical type of Ehlers-Danlos syndrome (EDS); the most common mutations lead to a non-functional COL5A1 allele. We characterized three skin fibroblast strains derived from patients affected by classical EDS caused by COL5A1 haploinsufficiency. As a typical clinical hallmark of EDS is the impaired wound healing, we analyzed the repair capability of fibroblasts in a monolayer wounding assay. The mutant fibroblast strains were unable to move into the scraped area showing then a marked delay in wound repair. In all the EDS strains, type V collagen was absent in the extracellular space, also leading to the lack of fibronectin fibrillar network and impairing the expression of alpha(2)beta(1) and alpha(5)beta(1) integrins. The abnormal integrin pattern inhibited the positive effect of insulin-like growth factor-binding protein-1 on cell migration, whereas the migratory capability remarkably improved in the presence of exogenous type V collagen.