2003 Fiscal Year Final Research Report Summary
Study of AP-1 in cyclosporine A-induced gingival overgrowth in rats.
| Project/Area Number |
14571983
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Periodontal dentistry
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| Research Institution | The University of Tokushima |
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Principal Investigator |
KATAOKA Masatoshi Univ.of Tokushima, Institute for Genome Research, Associate Professor, ゲノム機能研究センター, 助教授 (20224438)
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| Co-Investigator(Kenkyū-buntansha) |
SETO Hiroyuki Univ.of Tokushima, School of Dentistry, Assistant Professor, 歯学部, 助手 (90335802)
KIDO Jun-ichi Univ.of Tokushima, School of Dentistry, Assistant Professor, 歯学部, 助教授 (10195315)
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| Project Period (FY) |
2002 – 2003
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| Keywords | Cyclosporine A / Drug-induced gingival overgrowth / α2 integrin / Collagen phagocytosis / AP-1 / Fibroblast |
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| Research Abstract |
Cyclosporine A (CsA), an immunosuppresive agent, induces fibrous gingival overgrowth through reduction of collagen phagocytosis by fibroblasts. Distinct receptors are involved in the binding of collagen to fibroblasts in collagen phagocytosis, and α2β1 integrin serves as a specific receptor for type I collagen on fibroblasts. To elucidate the role ofa2f3l integrin in CsA-induced gingival overgrowth, we investigated collagen phagocytosis and α2β1 integrin expression in rat gingival overgrowth.
Fibroblasts were isolated from gingiva of rats fed a powdered diet containing or lacking CsA for 30 days. Flow cytometric analysis were performed to measure the collagen phagocytosis and the ct2 integrin expression in fibroblasts. Furthermore, total RNAs were isolated from fibroblasts, and the reverse transcriptase-polymerase chain reaction was employed to investigate the mRNA levels of cx2 integrin. And cDNA microarrays were performed to examine the various RNA expressions in CsA-treated and control rat gingival
In vitro collagen phagocytosis assay revealed that CsA-treated and control fibroblasts contained a mean of 13.5% and 36.1% phagocytic cells, respectively. CsA-treated fibroblasts had 28% lower expression of β1 integrin than that of control, and mRNA expression of α2 integrin in CsA-treated fibroblasts was apparently lower than in the controls, but the mRNA expression of f31 integrin was not affected. Furthermore, mRNA expression of c-fos in CsA-treated rat gingiva, a subunit of AP-1, which binds to enhancer region of a2 integrin and up-regulates of it expression, was suppressed to 49% of control rat gingiva.
These findings suggest that one etiological factor of gingival overgrowth may be inhibition of collagen phagocytosis by reducing cc2 integrin expression through the inhibition of c-fos mRNA in gingival fibroblasts.
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