The salivary glands are a major source of several factors, which play important roles in both oral and systemic organ homeostasis and wound healing. The roles of these factors, which include IGF-I, IGF-II, NGF, TGF alpha and beta, and EGF, has been well-studied. However, the fact that the salivary glands appear to be a major source of these growth factors present a interesting question both in the primary route of reentry into the system and the relative importance of these salivary- derived proteins systemically. In diabetic patients both (Type I and II) a major disease complication is diminished capacity of wound healing and in the oral cavity increased periodontal disease. A similar picture occurs in animal models of diabetes in there is also a progressive loss of growth factors from saliva in accordance with diabetes onset. Therefore, the investigators propose to look for the potential loss of salivary-derived growth factors associated with the observed decrease in wound healing capacity in diabetic patients. To accomplish this goal, they first plan to use the diabetic patient base of the University of Florida to investigate the changes in growth factor levels in patient saliva and serum after surgical procedures, as compared to healthy non-diabetic individuals undergoing similar procedures. Second, they intend to determine the influence of changes in growth factor levels in saliva on wound healing in the NOD mouse model for IDDM. With this, they intend to establish the NOD mouse as a viable model for this aspect of the disease and then to be able to employ this model to more thoroughly investigate the impact of decreased levels of salivary growth factors on experimentally introduced soft and hard tissue injuries. The results of these studies should elucidate the importance of salivary-derived growth factors on systemic homeostasis and wound repair and potentially provide insight into the viability of replacement strategies to combat several complications of human diabetes which may involve an underlying deficiency in wound repair mechanisms.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
1R01DE013290-01
Application #
2761275
Study Section
Special Emphasis Panel (ZRG2-NMS (03))
Project Start
1998-09-30
Project End
2002-07-31
Budget Start
1998-09-30
Budget End
1999-07-31
Support Year
1
Fiscal Year
1998
Total Cost
Indirect Cost
Name
University of Florida
Department
Dentistry
Type
Schools of Dentistry
DUNS #
073130411
City
Gainesville
State
FL
Country
United States
Zip Code
32611
Cha, Seunghee; Nagashima, Hiroyuki; Brown, Vinette B et al. (2002) Two NOD Idd-associated intervals contribute synergistically to the development of autoimmune exocrinopathy (Sjogren's syndrome) on a healthy murine background. Arthritis Rheum 46:1390-8
Cha, S; Peck, A B; Humphreys-Beher, M G (2002) Progress in understanding autoimmune exocrinopathy using the non-obese diabetic mouse: an update. Crit Rev Oral Biol Med 13:5-16
Cha, S; Nagashima, H; Peck, A B et al. (2002) IDD3 and IDD5 alleles from nod mice mediate Sjogren's syndrome-like autoimmunity. Adv Exp Med Biol 506:1035-9
Humphreys-Beher, M G; Brayer, J; Cha, S et al. (2002) Immunogenetics of autoimmune exocrinopathy in the nod mouse: more than meets the eye. Adv Exp Med Biol 506:999-1007
Brayer, J B; Cha, S; Nagashima, H et al. (2001) IL-4-dependent effector phase in autoimmune exocrinopathy as defined by the NOD.IL-4-gene knockout mouse model of Sjogren's syndrome. Scand J Immunol 54:133-40
Nagy, A; Nagashima, H; Cha, S et al. (2001) Reduced oral wound healing in the NOD mouse model for type 1 autoimmune diabetes and its reversal by epidermal growth factor supplementation. Diabetes 50:2100-4
Clarke, M Y; Brayer, J; Heintz, K et al. (2001) Differential absorption and distribution of epidermal growth factor and insulin-like growth factor in diabetic NOD mice. J Diabetes Complications 15:103-11
Brayer, J; Lowry, J; Cha, S et al. (2000) Alleles from chromosomes 1 and 3 of NOD mice combine to influence Sjogren's syndrome-like autoimmune exocrinopathy. J Rheumatol 27:1896-904
Nguyen, K H; Brayer, J; Cha, S et al. (2000) Evidence for antimuscarinic acetylcholine receptor antibody-mediated secretory dysfunction in nod mice. Arthritis Rheum 43:2297-306
Oxford, G E; Tayari, L; Barfoot, M D et al. (2000) Salivary EGF levels reduced in diabetic patients. J Diabetes Complications 14:140-5