cyclin-d1 and Gingival-Overgrowth

Cyclosporine A (CsA) increases β-catenin messenger RNA (mRNA) and protein expression. The present study demonstrates that Wnt/β-catenin signaling inhibits β-catenin degradation in the gingiva.. Forty 5-week-old male Sprague-Dawley rats were assigned to two study groups after healing from right maxillary molar extractions. The rats in the experimental group were fed 30 mg/kg CsA daily for 4 weeks, whereas the control rats were fed mineral oil. At the end of the study, all rats were sacrificed, and the gingivae were obtained. The gingival morphology after CsA treatment was evaluated by histology, and the genes related to Wnt/β-catenin signaling were initially screened by microarray. Polymerase chain reaction, Western blotting, and immunohistochemistry were used to examine the mRNA and protein expression of proliferating cell nuclear antigen, cyclin D1, E-cadherin, β-catenin, Dvl-1, glycogen synthase kinase-3β, axin-1, and adenomatous polyposis coli (APC). Phosphoserine and ubiquitinylated β-catenin were detected after immunoprecipitation.. In rats treated with CsA, overgrowth of gingivae was observed, and altered expression of genes related to Wnt/β-catenin signaling was detected by the microarray. The gingival mRNA and protein expression profiles for genes associated with Wnt/β-catenin signaling further confirmed the effect of CsA: β-catenin and Dvl-1 expression increased, but APC and axin-1 expression decreased. Western blotting and immunohistochemistry showed decreases in β-catenin serine phosphorylation (33/37) and ubiquitinylation in the gingivae of CsA-treated rats.. CsA-enhanced gingival β-catenin stability may be involved in gene upregulation or β-catenin degradation via the Wnt/β-catenin pathway.

Topics: Adaptor Proteins, Signal Transducing; Adenomatous Polyposis Coli Protein; Animals; Axin Protein; beta Catenin; Cadherins; Cyclin D1; Cyclosporine; Dishevelled Proteins; Gingiva; Gingival Overgrowth; Glycogen Synthase Kinase 3; Glycogen Synthase Kinase 3 beta; Immunosuppressive Agents; Male; Phosphoproteins; Phosphoserine; Proliferating Cell Nuclear Antigen; Random Allocation; Rats; Rats, Sprague-Dawley; RNA, Messenger; Wnt Signaling Pathway

It has previously been demonstrated that gingival fibroblasts derived from nifedipine-reactive patients (nifedipine responders) show a greater cell proliferation rate than those from nifedipine non-reactive patients (nifedipine non-responders) in the presence of 1 microM nifedipine. The aim of the present study was to characterize cell cycle differences between nifedipine responder and non-responder fibroblast cells and determine the effect of basic fibroblast growth factor (bFGF) on cell cycle progression. Further, the effect of bFGF on cyclins A, B1, D1, E, and CDKs 1, 2, 4, 6 mRNA expression in responder and non-responder cells was investigated. A population of nifedipine responder cells underwent progression to S and G2/M phases from G0/G1 phase in the presence of 10% fetal calf serum or 10 ng/ml bFGF was greater than nifedipine non-responder cells. mRNA expression of cyclins A, B1, D1, E and CDKs 1, 2, 4, 6 in the presence of 10 ng/ml bFGF was generally greater in nifedipine responder cells than non-responder cells. These results indicate that nifedipine responder cells may be more susceptible to growth factors such as bFGF with a resultant increase in expression of cyclins and CDKs in responder compared with non-responder cells.

Topics: CDC2 Protein Kinase; CDC2-CDC28 Kinases; Cell Cycle; Cell Division; Cells, Cultured; Cyclin A; Cyclin B; Cyclin B1; Cyclin D1; Cyclin E; Cyclin-Dependent Kinase 2; Cyclin-Dependent Kinase 4; Cyclin-Dependent Kinase 6; Cyclin-Dependent Kinases; Fibroblast Growth Factor 2; Fibroblasts; G1 Phase; G2 Phase; Gingiva; Gingival Overgrowth; Humans; Mitosis; Nifedipine; Proto-Oncogene Proteins; Resting Phase, Cell Cycle; S Phase