Reduced Oral Wound Healing in the NOD Mouse Model for Type 1 Autoimmune Diabetes and Its Reversal by Epidermal Growth Factor Supplementation

  1. Akos Nagy1,
  2. Hiroyuki Nagashima2,
  3. Seunghee Cha2,
  4. Gregory E. Oxford2,
  5. Tivadar Zelles1,
  6. Ammon B. Peck3 and
  7. Michael G. Humphreys-Beher2
  1. 1Department of Oral Biology, Semmelweis University Medical Center, Budapest, Hungary; and the Departments of
  2. 2Oral Biology and
  3. 3Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, Florida


    Using the NOD mouse, a model for type 1 diabetes, we examined how reduced concentrations of epidermal growth factor (EGF) in the saliva, after onset of type 1 diabetes, affect oral wound healing. Diabetic NOD/LtJ mice on insulin therapy, prediabetic NOD/LtJ, and age- and sex-matched BALB/cJ mice were given a cutaneous tongue punch and allowed to undergo normal healing. With diabetes onset and a reduction in saliva-derived growth factor levels, the rate of tongue wound healing was reduced compared with nondiabetic NOD/LtJ and healthy BALB/cJ mice. Addition of exogenous EGF to the drinking water did not accelerate the rate of healing in BALB/cJ or prediabetic NOD/LtJ; however, diabetic NOD/LtJ mice exhibited accelerated wound healing similar to healthy mice. These results demonstrate that loss of growth factors from saliva is associated with profoundly reduced oral wound healing, suggesting that therapeutic treatment with topical delivery may be beneficial to patients with type 1 diabetes and oral wound complications.


    • Address correspondence and reprint requests to Michael G. Humphreys-Beher, P.O. Box 100424, Department of Oral Biology, University of Florida, Gainesville, FL 32610. E-mail: h-beher{at}

      Received for publication 19 October 2000 and accepted in revised form 23 May 2001.

      ANOVA, analysis of variance; EGF, epidermal growth factor; NGF, nerve growth factor; RT-PCR, reverse transcriptase–polymerase chain reaction; TGF-α, transforming growth factor-α.

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