Upregulation of the Expression of Epidermal Growth Factor and Its Receptor in Gingiva Upon Cyclosporin A Treatment

Abstract

Higher expression of EGF and EGF-R upon CsA therapy was observed in OECM-1 epithelial cells of humans and in edentulous gingiva of rats. We suggest that CsA could upregulate gene and protein expression of EGF and EGF-R, and the upregulation may play a role in gingival overgrowth.

Cyclosporine A enhances apoptosis in gingival keratinocytes of rats and in OECM1 cells via the mitochondrial pathway

“…Therefore, we suggest that cyclosporine A can enhance cell apoptosis, via the Bax‐mediated mitochondrial pathway, in rat gingival keratinocytes and in OECM1 cells. The enhanced apoptosis in epithelia, in combination with the observed epithelial proliferation in our previous studies (6,47), might also suggest a rapid turnover of keratinocytes in gingiva during treatment with cyclosporine A.…”

“…An in vitro study has indicated that transforming growth factor beta‐1 induces p21 expression and apoptosis in a transforming growth factor beta‐1‐dependent manner (38). Enhanced expression of epidermal growth factor (EGF) and of its receptor after treatment with cyclosporine A was observed in edentulous gingivae of rats and in OECM1 cells in our laboratory (6). EGF can enhance cell proliferation and DNA synthesis and has been thought to be a mitogen for fibroblasts and for epithelial cells (39).…”

“…This effect may be related to the hyperplasia of gingival keratinocytes induced by cyclosporine A (3,4). Studies have found that cyclosporine A up‐regulates epithelial growth factor and keratinocyte growth factor (5,6), both of which are produced by epithelial cells. In our recent study, higher expressions of p21 mRNA and protein, via a p53‐independent pathway, were observed after treatment with cyclosporine A (7).…”

Expression and bioactivities of endothelin‐1 in gingiva during cyclosporine A treatment

“…In this study, the expression of PCNA was selected as the indicator for cell proliferation (11). After being stimulated with CsA (0, 100, 500 and 1000 ng/mL in DMSO) for 24 h, fibroblasts were fixed with 4% paraformadehyde and stained with anti‐PCNA antibodies (Santa Cruz Biotechnology, Inc., Santa Cruz, CA, USA) by immunocytochemistry (ICC).…”

Expression of p21 and p53 in rat gingival and human oral epithelial cells after cyclosporine A treatment

“…Whether p21 has any involvement in cyclosporine A‐induced gingival epithelial hyperplasia (via either the p53‐dependent or the p53‐independent pathway) has never been evaluated. In this study, the gene and protein expression of p21 after cyclosporine A therapy was examined in the overgrown edentulous gingivae of rats (7) and in an oral epithelial cell line (OECM1) (10), derived from a human oral epidermoid carcinoma, to elucidate the roles of p21 and p53 in cyclosporine A‐induced gingival epithelial alterations.…”