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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR036457-04
Application #
3157597
Study Section
General Medicine A Subcommittee 2 (GMA)
Project Start
1985-09-30
Project End
1990-08-31
Budget Start
1988-09-01
Budget End
1989-08-31
Support Year
4
Fiscal Year
1988
Total Cost
Indirect Cost
Name
University of Alabama Birmingham
Department
Type
Schools of Medicine
DUNS #
004514360
City
Birmingham
State
AL
Country
United States
Zip Code
35294
Irving-Rodgers, Helen F; Hummitzsch, Katja; Murdiyarso, Lydia S et al. (2010) Dynamics of extracellular matrix in ovarian follicles and corpora lutea of mice. Cell Tissue Res 339:613-24
Fingleton, Barbara; Powell, William C; Crawford, Howard C et al. (2007) A rat monoclonal antibody that recognizes pro- and active MMP-7 indicates polarized expression in vivo. Hybridoma (Larchmt) 26:22-7
Jiang, Xinnong; Multhaupt, Hinke; Chan, En et al. (2004) Essential contribution of tumor-derived perlecan to epidermal tumor growth and angiogenesis. J Histochem Cytochem 52:1575-90
Collawn, Sherry S; Woods, Anne; Couchman, John R (2003) Nondebridement of laser char after two carbon dioxide laser passes results in faster reepithelialization. Plast Reconstr Surg 111:1742-50
Jiang, Xinnong; Couchman, John R (2003) Perlecan and tumor angiogenesis. J Histochem Cytochem 51:1393-410
Tapanadechopone, P; Tumova, S; Jiang, X et al. (2001) Epidermal transformation leads to increased perlecan synthesis with heparin-binding-growth-factor affinity. Biochem J 355:517-27
Erickson, A C; Couchman, J R (2001) Basement membrane and interstitial proteoglycans produced by MDCK cells correspond to those expressed in the kidney cortex. Matrix Biol 19:769-78
Erickson, A C; Couchman, J R (2000) Still more complexity in mammalian basement membranes. J Histochem Cytochem 48:1291-306
Tapanadechopone, P; Hassell, J R; Rigatti, B et al. (1999) Localization of glycosaminoglycan substitution sites on domain V of mouse perlecan. Biochem Biophys Res Commun 265:680-90
Wu, R R; Couchman, J R (1997) cDNA cloning of the basement membrane chondroitin sulfate proteoglycan core protein, bamacan: a five domain structure including coiled-coil motifs. J Cell Biol 136:433-44

Showing the most recent 10 out of 50 publications