Cyclosporin-induced downregulation of the expression of E-cadherin during proliferation of edentulous gingival epithelium in rats.
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.
Tu
Hsiao-Pei
HP
Institute of Oral Biology, National Yang-Ming University, Taipei, Taiwan, Republic of China.
Chen
Yen-Teen
YT
Shieh
Yi-Shing
YS
Chin
Yu-Tang
YT
Huang
Ren-Yeong
RY
Yang
Shih-Fang
SF
Gau
Ching-Hwa
CH
Fu
Earl
E