Background: To examine the role of E-cadherin in epithelial hyperplasia of cyclosporin A (CsA)-induced gingival enlargement, mRNA and protein levels of E-cadherin, beta-catenin, proliferating cell nuclear antigen (PCNA), and Cyclin D1 were examined in the edentulous gingiva of rats following CsA treatment.
Methods: Three weeks after the extraction of all maxillary molars, 20 male Sprague-Dawley rats were assigned to a CsA-fed group (30 mg/kg daily) or a control group. Five rats per group were sacrificed at weeks 1 and 4. Edentulous ridge specimens were taken, and the expression levels of E-cadherin, beta-catenin, Cyclin D1, and PCNA mRNAs were estimated by reverse transcription-polymerase chain reaction (RT-PCR). Tissue specimens of the week 4 groups were examined using immunohistochemical (IHC) staining for proteins.
Results: The mRNA expression of E-cadherin was significantly weaker in the CsA-treated group than the control group at both times. Using IHC staining, a weaker level of membrane-bonded E-cadherin was also observed in the gingival epithelial cells in the CsA group than in controls. By contrast, significantly stronger beta-catenin and Cyclin D1 mRNA expressions and protein levels were found in CsA-treated rats than controls by RT-PCR and immunohistochemistry at week 4, whereas PCNA production was stronger at both times.
Conclusions: CsA treatment reduced the production of E-cadherin but increased the production of beta-catenin, Cyclin D1, and PCNA. Thus, CsA may downregulate E-cadherin gene expression, leading to the epithelial cell proliferation of gingival overgrowth.