Abstract

The basement membrane zone underlying the squamous epithelium of external tissues is ultrastructurally more complex than basement membrane zones of other tissues. In addition to lamina densa, these regions contain additional cellular elements such as the hemidesmosomes of the basal cells, anchoring filaments between the hemidesmosomes and the lamina densa, anchoring fibrils which appear to connect the lamina densa with the underlying connective tissue, and oxytalan fibers which may mediate the interaction of elastic elements with the lamina densa. The diseases of bullous pemphigoid and epidermolysis bullosa affect specific components in this region, and demonstrate the uniqueness of these structures to external tissues. As a first attempt to describe the network of molecules involved in the interaction of epithelial cells with molecules deep in the underlying matrix, we have produced monoclonal antibodies to yet unrecognized components. Two of these antibodies have been selected for further characterization. One of them have immunological and biochemical characteristics similar to those expected for anchoring filaments. The other has characteristics resembling oxytalan fibers. We have shown that these antigens are synthesized by specific cell populations and have demonstrated the feasibility of their chemical characterization. We propose to isolate and characterize these antigens in detail, to identify the antigen with ultrastructurally observed fibrous components of the basement membrane zone, and to investigate potential interactions between these components and other known connective tissue elements. We anticipate that the proposed studies will provide specific information regarding these basement membrane zone proteins and will help form a basis for the understanding of the structure of this unique region. This information will provide the background for forming hypotheses regarding the molecular events underlying the pathogenesis of epidermolysis bullosa and bullous pemphigoid.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR035689-02
Application #
3157342
Study Section
Pathobiochemistry Study Section (PBC)
Project Start
1985-09-23
Project End
1988-08-31
Budget Start
1986-09-01
Budget End
1987-08-31
Support Year
2
Fiscal Year
1986
Total Cost
Indirect Cost

  Institution

Name
Oregon Health and Science University
Department
Type
Schools of Medicine
DUNS #
009584210
City
Portland
State
OR
Country
United States
Zip Code
97239

  Publications

Amano, S; Scott, I C; Takahara, K et al. (2000) Bone morphogenetic protein 1 is an extracellular processing enzyme of the laminin 5 gamma 2 chain. J Biol Chem 275:22728-35
Koch, M; Olson, P F; Albus, A et al. (1999) Characterization and expression of the laminin gamma3 chain: a novel, non-basement membrane-associated, laminin chain. J Cell Biol 145:605-18
Champliaud, M F; Burgeson, R E; Jin, W et al. (1998) cDNA cloning and characterization of sciellin, a LIM domain protein of the keratinocyte cornified envelope. J Biol Chem 273:31547-54
Cserhalmi-Friedman, P B; Baden, H; Burgeson, R E et al. (1998) Molecular basis of non-lethal junctional epidermolysis bullosa: identification of a 38 basepair insertion and a splice site mutation in exon 14 of the LAMB3 gene. Exp Dermatol 7:105-11
Cheng, Y S; Champliaud, M F; Burgeson, R E et al. (1997) Self-assembly of laminin isoforms. J Biol Chem 272:31525-32
Wewer, U M; Thornell, L E; Loechel, F et al. (1997) Extrasynaptic location of laminin beta 2 chain in developing and adult human skeletal muscle. Am J Pathol 151:621-31
Gerecke, D R; Olson, P F; Koch, M et al. (1997) Complete primary structure of two splice variants of collagen XII, and assignment of alpha 1(XII) collagen (COL12A1), alpha 1(IX) collagen (COL9A1), and alpha 1(XIX) collagen (COL19A1) to human chromosome 6q12-q13. Genomics 41:236-42
Christiano, A M; Amano, S; Eichenfield, L F et al. (1997) Premature termination codon mutations in the type VII collagen gene in recessive dystrophic epidermolysis bullosa result in nonsense-mediated mRNA decay and absence of functional protein. J Invest Dermatol 109:390-4
Rousselle, P; Keene, D R; Ruggiero, F et al. (1997) Laminin 5 binds the NC-1 domain of type VII collagen. J Cell Biol 138:719-28
Champliaud, M F; Lunstrum, G P; Rousselle, P et al. (1996) Human amnion contains a novel laminin variant, laminin 7, which like laminin 6, covalently associates with laminin 5 to promote stable epithelial-stromal attachment. J Cell Biol 132:1189-98

Showing the most recent 10 out of 26 publications