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Growth factors and proliferation of cultured rat gingival cells in response to cyclosporin A
Author(s) -
Yoshida Takumasa,
Nagata Junji,
Yamane Akira
Publication year - 2005
Publication title -
journal of periodontal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.31
H-Index - 83
eISSN - 1600-0765
pISSN - 0022-3484
DOI - 10.1111/j.1600-0765.2004.00762.x
Subject(s) - growth factor , endocrinology , medicine , transforming growth factor , fibroblast , cell growth , fibroblast growth factor , biology , insulin like growth factor , messenger rna , receptor , cell culture , biochemistry , gene , genetics
Objective: The prominent side‐effect of cyclosporin A, an immunosuppressive drug, in oral tissues is gingival outgrowth, although the exact mechanism underlying this side‐effect is unclear. The main purposes of the present study were to determine whether cyclosporin A induced the gingival outgrowth by promoting proliferation of gingival cells and whether growth factors such as transforming growth factor‐βs (TGF‐βs), fibroblast growth factor‐2 (FGF‐2), platelet‐derived growth factors (PDGFs), and insulin‐like growth factors (IGFs) are involved in the possible changes in the proliferation of gingival cells induced by cyclosporin A. Methods: Cells isolated from rat gingival tissues were cultured with cyclosporin A or IGF‐I for 3 days. The effects of cyclosporin A or IGF‐I on the proliferation of cultured rat gingival cells were analyzed with a CellTiter 96 proliferation assay kit. The mRNA expression levels for TGF‐βs, FGF‐2, PDGFs, IGFs, insulin‐like growth factor receptors (IGFRs), and insulin‐like growth factor binding proteins (IGFBPs) in the rat gingival cells treated with cyclosporin A were measured using competitive reverse transcription–polymerase chain reaction (RT–PCR). Results: Cyclosporin A induced 23–25% ( p < 0.001) increases in the proliferation of rat gingival cells and approximately 130% ( p < 0.05) and 60% ( p < 0.05) elevations in the mRNA expression levels for TGF‐β1 and FGF‐2, respectively. On the other hand, exogenous IGF‐I induced 8–11% ( p < 0.05) increases in the proliferation, but cyclosporin A induced 30–80% ( p < 0.05–0.01) reductions in the mRNA expression levels for endogenous IGF‐I, IGFR1, IGFBP2, IGFBP3, IGFBP5, and IGFBP6. Conclusions: Cyclosporin A stimulates the proliferation of rat gingival cells. TGF‐β1 and FGF‐2 could be involved, but IGFs, IGFRs and IGFBPs could not be directly involved in this cyclosporin A induced‐stimulation of the gingival cell proliferation.