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Decreased expressions of thrombospondin 2 in cyclosporin A‐induced gingival overgrowth
Author(s) -
Koh Jeong Tae,
Kim Ok Joon,
Park Young Seob,
Kim Sun Hun,
Kim Won Jae,
Chung Hyun Ju,
Lee Shee Eun,
Jeong Byung Chul,
Jung Ji Yeon,
Kim Kyung Keun
Publication year - 2004
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.1600-0765.2004.00709.x
Subject(s) - thrombospondin , thrombospondin 1 , medicine , metalloproteinase , angiogenesis , matrix metalloproteinase
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.