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Collagen XVI – Background and State of the Art
Collagen XVI and chronic inflammatory Crohn's disease (CD)
Collagen XVI and Oral Squamous Cell Carcinoma (OSCC)
Relevant publications in context
The extracellular matrix of skin and cartilage is supported by fibrillar networks that vary in their molecular composition according to mechanical requirements. The structural diversity of fibrillar matrix aggregates arises from tissue specific incorporation and association of matrix components and different types of collagens.
Collagen XVI, a member of the family of fibril-associated collagens with interrupted triple helices comprises of three identical alpha-chains. It consists of ten multiple triple-helical domains (15-422 amino acids) that are interrupted by short, non-collagenous repeats (11-39 amino acids). The ability of associating with different structures tissue specifically is the remarkable feature of collagen XVI. In the dermo-epidermal junction it is associated with fibrillin-1 containing microfibrils, whereas in cartilage it shows connection to collagen II-containing cartilage fibrils.
We have expressed collagen XVI recombinantly in 293-EBNA-cells. This allows us to investigate and elucidate the influence of collagen XVI on fibrillar structures of the microfibrillar apparatus in D-banded cartilage fibrils. In-vitro binding studies with recombinant collagen XVI show high affinity to fibronectin, however weak interaction with fibrillin-1 and -2. In rotary shadowing, negative staining and atomic force microscopy (AFM) we have identified the structure of recombinant collagen XVI and the molecular size (Fig 1a, b).
Close assoziation to alpha 2 integrin in the dermal-epidermal junction zone (Fig. 1c, collagen XVI red, alpha 2 green, cell nuclei blue) was verified by ELISA-based binding assays to integrins alpha 1 and alpha 2 which demonstrated high affinity binding of collagen XVI to integrins.
In Crohn’s disease (CD) the stress-shield of intestinal subepithelial myofibroblasts (ISEMF) provided by intact tissue is disturbed due to inflammation and thus, cells start with remodelling activities. This is characterized by increased numbers of collagen-producing ISEMF causing an uncontrolled, irreversible wound-healing response to the chronic inflammation of the gastrointestinal tract. Reconstitution of the original ECM leads ISEMF to exit this cycle. In contrast, during fibrosis, ISEMF persist. It is known that ISEMF produce and deposit collagen types I, III, IV and V; however synthesis and the role of fibrillar peripheral molecules like collagen type XVI have not been addressed yet. Here, we have analyzed the distribution of collagen XVI in the normal and inflamed bowel wall, its gene and protein expression by ISEMF of different inflammation stages, the cell-matrix interactions in different phases of the inflammatory process and their effect on cell spreading, proliferation and migration. Collagen XVI is deposited in the submucosa of the intestinal wall where it co-localizes with fibrillin-1 and integrin alpha 1. ISEMF reveal increasing gene and protein expression of collagen XVI concurrent to increasing inflammation. ISEMF reveal more mature focal adhesion contacts when seeded on collagen XVI resulting in an extensive cell spreading. This involves recruitment of α1b1 integrin, which shows increased cell surface expression on ISEMF in late stages of inflammation. We assume that collagen XVI promotes persistence of ISEMF in the normal and, even stronger in the inflamed bowel wall by stabilizing focal adhesion contacts via cell-matrix interaction preferentially through recruitment of α1ß1 integrin into the tips of the focal adhesion contacts.
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