Abstract

The control of proliferation of corneal endothelial cells by EGF will be analyzed. The relevance of EGF binding, internalization, and degradation for the induction of cell division will be defined. We will also study the possible binding of EGF to nuclear receptor sites versus cell surface receptor sites. The effect of EGF on the synthesis of cytoplasmic proteins, which may be involved in supporting the progression of the cells through the G1 phase of the cell cycle, will be studied as a function of the cell cycle and of cell density. The possibility that, at confluence, a restriction in the cell surface receptor lateral mobility could prevent the internalization of EGF receptor complexes and their subsequent triggering of cell division will be investigated. The role of the extracellular matrix (ECM) in events controlling corneal endothelial cell proliferation and differentiation will be analyzed using two cell strains of corneal endothelial cells. One expresses its normal phenotype in vitro when maintained in the presence of FGF, while the other, maintained in the absence of FGF, no longer expresses it. The composition, distribution, and polarity of secretion of collagen types produced by sparse versus confluent cultures of corneal endothelial cells maintained in the presence or absence of FGF or EGF will be analyzed using indirect immunofluorescence techniques. This will be followed by the biochemical analysis of the composition and production of collagen produced by sparse versus confluent cultures of corneal endothelial cells maintained in the presence or absence of EGF or FGF. The direct modulation of collagen synthesis by FGF and EGF when added to cultures which no longer express their normal phenotype at confluence will be analyzed. The nature of the permissive effect of the ECM on cell proliferation and differentiation will be studied by investigating the proliferation and differentiation on dishes coated with an ECM produced by bovine corneal endothelial cells of cell types of the ocular system which do not proliferate (human corneal endothelial cells) or differentiate (corneal epithelial cells) on plastic.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY002186-08
Application #
3256546
Study Section
Visual Sciences A Study Section (VISA)
Project Start
1977-12-01
Project End
1985-11-30
Budget Start
1984-12-01
Budget End
1985-11-30
Support Year
8
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
University of California San Francisco
Department
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143

  Publications

Gospodarowicz, D; Abraham, J A; Schilling, J (1989) Isolation and characterization of a vascular endothelial cell mitogen produced by pituitary-derived folliculo stellate cells. Proc Natl Acad Sci U S A 86:7311-5
Gospodarowicz, D; Ferrara, N; Haaparanta, T et al. (1988) Basic fibroblast growth factor: expression in cultured bovine vascular smooth muscle cells. Eur J Cell Biol 46:144-51
Adashi, E Y; Resnick, C E; Croft, C S et al. (1988) Basic fibroblast growth factor as a regulator of ovarian granulosa cell differentiation: a novel non-mitogenic role. Mol Cell Endocrinol 55:7-14
Schweigerer, L; Ferrara, N; Haaparanta, T et al. (1988) Basic fibroblast growth factor: expression in cultured cells derived from corneal endothelium and lens epithelium. Exp Eye Res 46:71-80
Schweigerer, L; Malerstein, B; Neufeld, G et al. (1987) Basic fibroblast growth factor is synthesized in cultured retinal pigment epithelial cells. Biochem Biophys Res Commun 143:934-40
Schweigerer, L; Neufeld, G; Gospodarowicz, D (1987) Basic fibroblast growth factor as a growth inhibitor for cultured human tumor cells. J Clin Invest 80:1516-20
Schweigerer, L; Neufeld, G; Gospodarowicz, D (1987) Basic fibroblast growth factor is present in cultured human retinoblastoma cells. Invest Ophthalmol Vis Sci 28:1838-43
Massoglia, S L; Kenney, J S; Gospodarowicz, D J (1987) Characterization of murine monoclonal antibodies directed against basic fibroblast growth factor. J Cell Physiol 132:531-7
Schweigerer, L; Neufeld, G; Friedman, J et al. (1987) Basic fibroblast growth factor: production and growth stimulation in cultured adrenal cortex cells. Endocrinology 120:796-800
Schweigerer, L; Neufeld, G; Friedman, J et al. (1987) Capillary endothelial cells express basic fibroblast growth factor, a mitogen that promotes their own growth. Nature 325:257-9

Showing the most recent 10 out of 27 publications