Type VI Collagen Regulates Dermal Matrix Assembly and Fibroblast Motility

Abstract

Type VI collagen is a non-fibrillar collagen expressed in many connective tissues and implicated in extracellular matrix (ECM) organisation. 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 fibres 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-cellularised 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 behaviour and may play an important role in wound healing and tissue regeneration.Journal of Investigative Dermatology accepted article preview online, 09 September 2015. doi:10.1038/jid.2015.352.

Topical Fibronectin Improves Wound Healing of Irradiated Skin

“…Collagen VI, like fibronectin, is an ECM protein downregulated in irradiated skin (fold-change 0.54). In a study of cell-derived matrices deficient in the protein, collagen VI was critically associated with assembly of the dermal matrix and motility of resident fibroblasts, suggesting that downregulation may limit wound healing 39 . P27(Kip1) is an enzyme inhibitor that controls cell cycle progression and has been shown to play a supervisory role in preventing hyperproliferation during tissue repair 40 .…”

Keloids, Spontaneous or After Minor Skin Injury: Importance of Not Missing Bethlem Myopathy

“…Collagen VI is a critical component in maintaining the integrity of the skin, promoting roles such as organization and communication between cells. Recently, it has been found that collagen VI regulates the organization and composition of de novo ECM within the skin, suggesting a key role in wound healing and tissue repair (15). Therefore, its alteration appears to make skin susceptible to a variety of abnormalities, including spontaneous keloids, which are part of the clinical spectrum of skin alterations related to COL6-RD.…”

Scarring vs. functional healing: Matrix-based strategies to regulate tissue repair

“…Collagen VI deficient matrices are thinner and contain less total collagen than matrices derived from healthy individuals. Collagen VI also affects cell spreading and migration [10]. Interestingly, macrophages secrete collagen type VI to modify cell-matrix interactions during wound healing [11].…”