Type VI collagen regulates dermal matrix assembly and fibroblast motility

Georgios Theocharidis, Zoe Drymoussi, Alex Kao, Asa Barber, David A. Lee, Kristin M. Braun, John T. Connelly

    Research output: Contribution to journalArticlepeer-review

    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.
    Original languageEnglish
    Pages (from-to)74-83
    Number of pages10
    JournalJournal of Investigative Dermatology
    Volume136
    Issue number1
    Early online date9 Sep 2015
    DOIs
    Publication statusPublished - Jan 2016

    Keywords

    • RCUK
    • EPSRC
    • BBSRC
    • BB/J000914/1

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