The major objective of this study is to develop a comprehensive understanding of the keratinization process in order to more fully understand the numerous disorders which involve epidermis, hair and nail. Since the fibrous proteins play a major role emphasis will be placed on them, but other important structural components, keratohyalin and cornified cell envelope, will also be investigated. These studies will be done in whole tissue as well as in cultured epidermal cells with the aim of using epidermal cell culture to study the metabolic disturbances in a number of disorders of keratinization including psoriasis and several types of ichthyosis. Epidermal cell culture will be used to study mechanism of disease and the effect of various hormones and chemicals on normal epidermal cells as well as diseased cells. This will include basal cell carcinoma. The epidermal enzyme which converts peptide bound argininge to peptide bound citruline will be purified and characterized and the natural substrates will be identified. The precursors of the cornified envelope of human keratinocytes will be identified in cultured cells and whole tissue by use of labelled probes as well as immunologic techniques. The procursors of keratohyalin granules in cultured rat epidermis will be identified by labelled histidine incorporation and immunologic techniques. The factors influencing the composition of fibrous proteins will be investigated. We shall ccntinue our studies of inherited disorders of keratinization so that patient material will be available for laboratory study.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR006838-24
Application #
3154660
Study Section
General Medicine A Subcommittee 2 (GMA)
Project Start
1975-01-01
Project End
1989-12-31
Budget Start
1986-01-01
Budget End
1986-12-31
Support Year
24
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02199
Baden, H P; Goldaber, M L; Kvedar, J C (1992) Keratinocytes stimulate prostaglandin I2 synthesis by 3T3 cells and exhibit enhanced cornification when exposed to prostaglandin I2 analogues. J Cell Physiol 150:269-75
Kvedar, J C; Manabe, M; Phillips, S B et al. (1992) Characterization of sciellin, a precursor to the cornified envelope of human keratinocytes. Differentiation 49:195-204
Kvedar, J C; Baden, H P (1991) Nail changes in cutaneous disease. Semin Dermatol 10:65-70
Baden, H P; Kubilus, J K; Phillips, S B (1987) Characterization of monoclonal antibodies generated to the cornified envelope of human cultured keratinocytes. J Invest Dermatol 89:454-9
Baden, H P; Kubilus, J; Phillips, S B et al. (1987) A new class of soluble basic protein precursors of the cornified envelope of mammalian epidermis. Biochim Biophys Acta 925:63-73