Type XV collagen exhibits a widespread distribution in human tissues but a distinct localization in basement membrane zones

Abstract

The collagen family of proteins consists of 19 types encoded by 33 genes. One of the more recently discovered collagens is the alpha1 chain of type XV. Type XV collagen is comprised of a 577-amino-acid, highly interrupted, triple-helical region that is flanked by amino and carboxy noncollagenous domains of 555 and 256 residues, respectively. To address questions of where this collagen is localized and what its function may entail, we produced a bacteria-expressed recombinant protein representing the first half of the type XV collagen carboxy-terminal domain in order to generate highly specific polyclonal antisera. Immunoscreening of an expression library with the affinity-purified antibody revealed three clones coding for part of the type XV triple-helical region and the entire noncollagenous carboxy-terminus. Western blot analysis of human tissue homogenates identified a 116-kDa collagenase-sensitive protein and a 27-kDa collagenase-resistant fragment, whose electrophoretic mobilities were unchanged in the presence and absence of reductant. Northern blot hybridization to human tissue RNAs indicated that type XV has a prevalent and widespread distribution. To determine the precise localization of type XV collagen, immunohistochemical analyses at the light- and electron-microscopic levels were performed. Type XV exhibited a surprisingly restricted and uniform presence in many human tissues as evidenced by a strong association with vascular, neuronal, mesenchymal, and some epithelial basement membrane zones. These data suggest that type XV collagen may function in some manner to adhere basement membrane to the underlying connective tissue stroma.

Basement Membranes: Cell Scaffoldings and Signaling Platforms

“…Mutations of the gene for type XVIII collagen are a cause of Knobloch syndrome, characterized by vitreoretinal degeneration and occipital encephalocele. Type XV collagen is a nonfibrillar collagen with multiple interruptions of the gly-x-y sequence and with attachments to both heparan sulfate and chondroitin sulfate chains (Myers et al 1996;Myers et al 2003). Found at the basement membrane/stromal interface, it is also thought to serve as a link to the stroma (Myers et al 1997).…”

Complete Suppression of Tumor Formation by High Levels of Basement Membrane Collagen

“…Fresh-frozen sections of the tumors produced by the nude mouse xenografts were stained with a primary rabbit antibody raised against collagen XV or with a monoclonal antibody against the endothelial component CD31, following published techniques (17). Sections were counterstained with H&E.…”

Novel endothelial cell markers in hepatocellular carcinoma

“…35 COL15A1 was reported to stain capillary endothelium. 36,37 Endothelial differentiation gene 1 (EDG1) was cloned from human umbilical vein endothelial cells and was implicated in differentiation of endothelial cells and vascular maturation. 38,39 PODXL, a transmembrane protein with a similar structure to CD34, is expressed in the foot processes of glomerular podocytes and endothelial cells of normal kidney.…”