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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Decreased expressions of thrombospondin 2 in cyclosporin A-induced gingival overgrowth.

OBJECTIVES: Cyclosporin A (CsA) is known to elicit fibrous gingival overgrowth with changes of blood vessel profiles. In this study, we examined the expression of several angiogenic and angiostatic genes during the development of CsA-induced gingival overgrowth. METHODS: For the development of gingival overgrowth, Sprague-Dawley rats received subcutaneous injections of CsA in daily doses of 5, 10, 15 mg/kg body weight for 6 weeks, and another group received 10 mg/kg of CsA for 3, 6, and 12 weeks. Human gingival tissues were obtained from three CsA-treated patients following the gingivectomy procedure and from three healthy patients following the crown-lengthening procedure as a control. Gingival fibroblasts were isolated from the healthy gingival tissues of the rat or the human, and cultured with 250-1000 ng/ml of CsA. RESULTS: Reverse transcription-polymerase chain reaction (RT-PCR) analyses showed that expressions of some angiogenic genes such as angiopoietin 1, basic fibroblast growth factor, and vascular endothelial growth factor, and angiostatic genes such as angiopoietin 2, brain-specific angiogenesis inhibitor 1 and 2, and thrombospondin 1 were not changed significantly in both gingival tissues and cultured fibroblast cells under the CsA treatments. However, expression of thrombospondin 2 ( TSP2) decreased dose- and time-dependently in rat and human gingival tissues. Western blot analyses showed that the expression of TSP2 protein was dose-dependently reduced by the CsA treatments in human cultured gingival fibroblasts. CONCLUSIONS: These results indicate that the decrease in angiostatic TSP2 expression may be attributed to the CsA-induced gingival vascularization rather than to the increased expression of angiogenic genes. It suggests that TSP2 is involved in the development of CsA-induced gingival overgrowth with the gingival vascularization.[1]


  1. Decreased expressions of thrombospondin 2 in cyclosporin A-induced gingival overgrowth. Koh, J.T., Kim, O.J., Park, Y.S., Kim, S.H., Kim, W.J., Chung, H.J., Lee, S.E., Jeong, B.C., Jung, J.Y., Kim, K.K. J. Periodont. Res. (2004) [Pubmed]
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