The basic hypothesis underlying the proposed studies is that lipids found in the superficial layers of oral epithelium increase its diffusional resistance, and thereby, limit the penetration of a variety of potentially harmful agents including microbial toxins and enzymes, antigens from foods, and toxins and carcinogens from a variety of sources. Epithelial permeability varies regionally, and this is reflected in the distribution of certain diseases including leukoplakias and cancer. To establish an ultrastructural and molecular basis for understanding this regional variation in permeability and its relationship to oral health, several studies employing the well established porcine model system are proposed. Membrane-coated granules, the barrier precursors in both keratinized and nonkeratinized epithelia, will be isolated, and the lipids and some enzymes thought to function in barrier maturation will be characterized. Barrier layers will be isolated by tryptic digestion, and the compositions and structures of the lipids will be determined by chemical, chromatographic and spectroscopic methods. Barrier ultrastructure will be examined using a RuO4 method, and changes in organization, as well as in lipid composition and structure, accompanying the progressive perturbation of barrier function by essential fatty acid deficiency will be examined. The proposed studies include the first attempts to isolate and biochemically characterize membrane-coating granules from oral epithelium. This will provide basic information on lipid accumulation and the enzymatic basis for barrier assembly. A more complete knowledge of the barrier components and their modulation during barrier impairment would be useful in explaining the regional variation in permeability and disease occurrence and could ultimately be useful in explaining individual variation in susceptibility to disease. These studies are important in view of the possible role of impaired barrier function in the etiology of a variety of oral diseases and could ultimately lead to diagnostic methods and to strategies for preventing disease by augmenting barrier function.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE010516-02
Application #
2131405
Study Section
Oral Biology and Medicine Subcommittee 1 (OBM)
Project Start
1993-09-01
Project End
1996-08-31
Budget Start
1994-09-01
Budget End
1995-08-31
Support Year
2
Fiscal Year
1994
Total Cost
Indirect Cost
Name
University of Iowa
Department
Dentistry
Type
Schools of Dentistry
DUNS #
041294109
City
Iowa City
State
IA
Country
United States
Zip Code
52242
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Wertz, P W; van den Bergh, B (1998) The physical, chemical and functional properties of lipids in the skin and other biological barriers. Chem Phys Lipids 91:85-96
Madison, K C; Sando, G N; Howard, E J et al. (1998) Lamellar granule biogenesis: a role for ceramide glucosyltransferase, lysosomal enzyme transport, and the Golgi. J Investig Dermatol Symp Proc 3:80-6
Attar, P S; Wertz, P W; McArthur, M et al. (1997) Inhibition of retinoid signaling in transgenic mice alters lipid processing and disrupts epidermal barrier function. Mol Endocrinol 11:792-800
Squier, C A; Kremer, M; Wertz, P W (1997) Continuous flow mucosal cells for measuring the in-vitro permeability of small tissue samples. J Pharm Sci 86:82-4
Whittle, S; Swartzendruber, D C; Kremer, M et al. (1997) Lipids of hamster cheek pouch epithelium. Lipids 32:961-4
Wertz, P W (1997) Integral lipids of hair and stratum corneum. EXS 78:227-37
Law, S; Wertz, P W; Swartzendruber, D C et al. (1995) Regional variation in content, composition and organization of porcine epithelial barrier lipids revealed by thin-layer chromatography and transmission electron microscopy. Arch Oral Biol 40:1085-91
Swartzendruber, D C; Manganaro, A; Madison, K C et al. (1995) Organization of the intercellular spaces of porcine epidermal and palatal stratum corneum: a quantitative study employing ruthenium tetroxide. Cell Tissue Res 279:271-6
Law, S L; Squier, C A; Wertz, P W (1995) Free sphingosines in oral epithelium. Comp Biochem Physiol B Biochem Mol Biol 110:511-3

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