title: Type VI Collagen Regulates Dermal Matrix Assembly and Fibroblast Motility.
abstract: Type VI collagen is a nonfibrillar collagen expressed in many connective tissues and implicated in extracellular matrix (ECM) organization. We hypothesized that type VI collagen regulates matrix assembly and cell function within the dermis of the skin. In the present study we examined the expression pattern of type VI collagen in normal and wounded skin and investigated its specific function in new matrix deposition by human dermal fibroblasts. Type VI collagen was expressed throughout the dermis of intact human skin, at the expanding margins of human keloid samples, and in the granulation tissue of newly deposited ECM in a mouse model of wound healing. Generation of cell-derived matrices (CDMs) by human dermal fibroblasts with stable knockdown of COL6A1 revealed that type VI collagen-deficient matrices were significantly thinner and contained more aligned, thicker, and widely spaced fibers than CDMs produced by normal fibroblasts. In addition, there was significantly less total collagen and sulfated proteoglycans present in the type VI collagen-depleted matrices. Normal fibroblasts cultured on de-cellularized CDMs lacking type VI collagen displayed increased cell spreading, migration speed, and persistence. Taken together, these findings indicate that type VI collagen is a key regulator of dermal matrix assembly, composition, and fibroblast behavior and may play an important role in wound healing and tissue regeneration.
authors.affiliation: Centre for Cell Biology and Cutaneous Research, Barts and the London School of Medicine and Dentistry, Queen Mary, University of London, London, United Kingdom.
authors.forename: Georgios
authors.initials: G
authors.lastname: Theocharidis
authors.affiliation: Centre for Cell Biology and Cutaneous Research, Barts and the London School of Medicine and Dentistry, Queen Mary, University of London, London, United Kingdom.
authors.forename: Zoe
authors.initials: Z
authors.lastname: Drymoussi
authors.affiliation: Institute of Bioengineering, School of Engineering and Materials Science, Queen Mary, University of London, London, United Kingdom.
authors.forename: Alexander P
authors.initials: AP
authors.lastname: Kao
authors.affiliation: Institute of Bioengineering, School of Engineering and Materials Science, Queen Mary, University of London, London, United Kingdom; School of Engineering, University of Portsmouth, Portsmouth, United Kingdom.
authors.forename: Asa H
authors.initials: AH
authors.lastname: Barber
authors.affiliation: Institute of Bioengineering, School of Engineering and Materials Science, Queen Mary, University of London, London, United Kingdom.
authors.forename: David A
authors.initials: DA
authors.lastname: Lee
authors.affiliation: Centre for Cell Biology and Cutaneous Research, Barts and the London School of Medicine and Dentistry, Queen Mary, University of London, London, United Kingdom.
authors.forename: Kristin M
authors.initials: KM
authors.lastname: Braun
authors.affiliation: Centre for Cell Biology and Cutaneous Research, Barts and the London School of Medicine and Dentistry, Queen Mary, University of London, London, United Kingdom. Electronic address: j.connelly@qmul.ac.uk.
authors.forename: John T
authors.initials: JT
authors.lastname: Connelly
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D024142:Collagen Type VI / Q000378:metabolism*; D000078404:Epidermal Cells; D004817:Epidermis / Q000648:ultrastructure; D005109:Extracellular Matrix / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology* / Q000502:physiology; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007627:Keloid / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D023421:Models, Animal; D012016:Reference Values; D012680:Sensitivity and Specificity
chemical_list: D024142:Collagen Type VI