title: In vivo evidence for a bridging role of a collagen V subtype at the epidermis-dermis interface.
abstract: Collagen V is the defective product in most cases of classical Ehlers-Danlos syndrome (EDS), a connective tissue disorder typically characterized by skin fragility and abnormal wound healing. Collagen V assembles into diverse molecular forms. The predominant α1(V)(2)α2(V) heterotrimer controls fibrillogenesis in skin and other tissues. The α1(V)(3) minor form is thought to occur in skin, but its function is unknown. To elucidate its role, we generated transgenic mice that overexpress the human α1(V)(3) homotrimer in the epidermis. The transgene-derived product is deposited as thin unstriated fibrillar material in the basement membrane zone of embryonic and perinatal epidermis and hair follicles. Accumulation of α1(V)(3)-containing fibrils leads to ultrastructural modifications at the epidermis-dermis interface and provokes changes in biomechanical properties, although not statistically significant. Using superparamagnetic immunobeads to isolate authentic suprastructures and protein-binding assays, we demonstrate that the homotrimer is part of a protein network containing collagen IV, laminin-111, and the dermal collagen VI. Our data show that the homotrimer serves as a bridging molecule that contributes to the stabilization of the epidermal-dermal interface. This finding strongly suggests that collagen V may be expressed in skin as different subtypes with important but distinct roles in matrix organization and stability.
authors.affiliation: Institut de Génomique Fonctionnelle de Lyon, ENS de Lyon, UMR CNRS 5242, SFR BioSciences Gerland, Lyon, France.
authors.forename: Christelle
authors.initials: C
authors.lastname: Bonod-Bidaud
authors.forename: Muriel
authors.initials: M
authors.lastname: Roulet
authors.forename: Uwe
authors.initials: U
authors.lastname: Hansen
authors.forename: Ahmed
authors.initials: A
authors.lastname: Elsheikh
authors.forename: Marilyne
authors.initials: M
authors.lastname: Malbouyres
authors.forename: Sylvie
authors.initials: S
authors.lastname: Ricard-Blum
authors.forename: Clément
authors.initials: C
authors.lastname: Faye
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Vaganay
authors.forename: Patricia
authors.initials: P
authors.lastname: Rousselle
authors.forename: Florence
authors.initials: F
authors.lastname: Ruggiero
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D024062:Collagen Type V / Q000737:chemistry / Q000502:physiology*; D020405:Dermis / Q000378:metabolism*; D004817:Epidermis / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D055503:Protein Multimerization; D012867:Skin / Q000648:ultrastructure
chemical_list: C530725:COL5A1 protein, human; D024062:Collagen Type V