Type VI Collagen Regulates Dermal Matrix Assembly and Fibroblast Motility

Journal article

Theocharidis, G, Drymoussi, Z, Kao, AP, Barber, AH, Lee, DA, Braun, KM and Connelly, JT (2016). Type VI Collagen Regulates Dermal Matrix Assembly and Fibroblast Motility. Journal of Investigative Dermatology. 136 (1), pp. 74-83. https://doi.org/10.1038/JID.2015.352
AuthorsTheocharidis, G, Drymoussi, Z, Kao, AP, Barber, AH, Lee, DA, Braun, KM and Connelly, JT
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.

Keywords1103 Clinical Sciences; 1112 Oncology And Carcinogenesis; Dermatology & Venereal Diseases
Year2016
JournalJournal of Investigative Dermatology
Journal citation136 (1), pp. 74-83
PublisherElsevier
ISSN0022-202X
Digital Object Identifier (DOI)https://doi.org/10.1038/JID.2015.352
Publication dates
Print04 Jan 2016
Publication process dates
Deposited22 Aug 2018
Accepted17 Aug 2015
Accepted author manuscript
License
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Open
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