title: 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.
authors.affiliation: Department of Biochemistry A. Castellani, University of Pavia, Pavia, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Viglio
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Zoppi
authors.forename: Antonella
authors.initials: A
authors.lastname: Sangalli
authors.forename: Angelo
authors.initials: A
authors.lastname: Gallanti
authors.forename: Sergio
authors.initials: S
authors.lastname: Barlati
authors.forename: Monica
authors.initials: M
authors.lastname: Mottes
authors.forename: Marina
authors.initials: M
authors.lastname: Colombi
authors.forename: Maurizia
authors.initials: M
authors.lastname: Valli
mesh_terms: D000483:Alleles; D016022:Case-Control Studies; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D024062:Collagen Type V / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D004535:Ehlers-Danlos Syndrome / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D005109:Extracellular Matrix / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000502:physiology*; D038982:Integrin alpha2beta1 / Q000378:metabolism; D039081:Integrin alpha5beta1 / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D014945:Wound Healing / Q000502:physiology
chemical_list: C530725:COL5A1 protein, human; D024062:Collagen Type V; D018970:Insulin-Like Growth Factor Binding Protein 1; D038982:Integrin alpha2beta1; D039081:Integrin alpha5beta1