Basement membranes are specialized zones of connective tissue underlying parenchymal cells and separating them from supporting connective tissues. They are composed of a number of macromolecules which interact with each other and with cell surfaces. Functionally they not only provide support and a selective filter but, through cell surface interactions, profoundly influence cell behavior such as growth, migration and differentiation. Heparan sulfate proteoglycan has been identified as an important basement membrane constituent and is implicated in control of basement membrane permeability. We have also identified and partially characterized a basement membrane-specific chondroitin sulfate proteoglycan synthesized by the PYS-2 cell line. Antibodies have been raised against this and the heparan sulfate proteoglycan, purified from bulk cultures, and these stain many mammalian basement membranes. In this proposal we aim to further characterize the proteoglycans and survey their distribution in skin and other basement membranes, with particular emphasis on the embryonic development and ultrastructural studies. The antisera already raised will be exhaustively characterized and monoclonal antibodies will be raised against the PYS-2 chondroitin sulfate proteoglycan. These will assist in immunohistochemical and structural analysis of this newly recognized basement membrane component. The intermolecular interactions between the PYS-2 proteoglycans and other basement membrane macromolecules will also be investigated. It is intended that data concerning the role of basement membrane proteoglycans in the dermal-epidermal junction will be gained which may be of future significance in the study of a wide range of skin diseases where lesions at the basement membrane are an integral part of the pathological process.
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