Oral mucosa and skin show marked regional variation in structure which appears to be related to regional differences in function. Epithelia are continuously regenerating structures and there is evidence to suggest that the connective tissues beneath the epithelium continue, throughout life, to exert directive and permissive influences which maintain normal growth and the regional specificity of structure of epithelia. Many of the adverse pathological processes occurring in the oral cavity, ranging from periodontal disease to carcinoma are associated with, or are casually related to, changes in the maintenance of epithelial structure. Information which leads to findings indicate that (a) epithelial histodifferentiation (as characterized by patterns of keratin synthesis, rates of cell division and establishment of tissue architecture) can be directed by subepithelial connective tissue and (b) that in order to express their intrinsic phenotype, adult epithelia require permissive influences provided by subepithelial, but not deep, connective tissue. The objectives of the proposed reseach are (a) to use standardized in vitro conditions for analyzing the influence of permissive and directive connective tissue effects on epithelia, (b) to examine the ability of neonatal and transformed cells to induce functional changes in connective tissue, (c) to re-examine epithelial migration and differentiation in relation to concepts of dermal permissiveness, and (d) to examine the structural stability of the gingival sulcus in relation to epithelial-mesenchymal interactions. These problems will be investigated using murine and human mucosal and epidermal specimens, either in vitro or transplanted to histocompatible or immunodeficient mice. Specimens will be analyzed by biochemical, ultrastructural, immunofluorescent, and cell kinetic techniques.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE005190-08
Application #
3219278
Study Section
Oral Biology and Medicine Study Section (OBM)
Project Start
1978-12-01
Project End
1989-08-31
Budget Start
1987-09-01
Budget End
1988-08-31
Support Year
8
Fiscal Year
1987
Total Cost
Indirect Cost
Name
University of Iowa
Department
Type
Schools of Dentistry/Oral Hygn
DUNS #
041294109
City
Iowa City
State
IA
Country
United States
Zip Code
52242
Lu, H; Mackenzie, I C; Levine, A E (1997) Transforming growth factor-beta response and expression in junctional and oral gingival epithelial cells. J Periodontal Res 32:682-91
Mackenzie, I; Rittman, G; Bohnert, A et al. (1993) Influence of connective tissues on the in vitro growth and differentiation of murine epidermis. Epithelial Cell Biol 2:107-19
Mackenzie, I C; Dabelsteen, E; Mandel, U (1989) Expression of blood group antigen-related carbohydrates by human gingival epithelia. J Periodontal Res 24:289-97
Hill, M W; Mackenzie, I C (1989) The influence of subepithelial connective tissues on epithelial proliferation in the adult mouse. Cell Tissue Res 255:179-82
Mackenzie, I C; Dabelsteen, E (1987) Connective tissue influences on the expression of epithelial cell-surface antigens. Cell Tissue Res 248:137-41
Mackenzie, I C (1987) Nature and mechanisms of regeneration of the junctional epithelial phenotype. J Periodontal Res 22:243-5
Loning, T H; Mackenzie, I C (1986) Immunohistochemical studies of basal cell carcinomas transplanted into nude mice. Arch Dermatol Res 279:37-43
Mackenzie, I; Howlett, J; Ranasinghe, A (1985) An organ culture model for examining epidermal desquamation. J Invest Dermatol 85:314-8