Tanshinone IIA treatment alleviated the rat gingival connective tissue overgrowth induced by cyclosporine A
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BACKGROUND AND OBJECTIVE: The use of cyclosporine A induces fibrous enlargement of the gingival connective tissue. Existing treatment modalities, although effective, do not necessarily prevent the recurrence of the lesion. Emerging evidence indicates that tanshinone IIA (Tan IIA) could effectively attenuate a variety of fibrotic diseases. The present research aims to assess whether Tan IIA can effectively alleviate the gingival fibrous overgrowth induced by cyclosporine A. MATERIAL AND METHODS: Forty-five Wistar rats were divided into the no-treatment control group, cyclosporine A-treated group and the group treated with a combination of cyclosporine A and Tan IIA. Paraffin-embedded sections of mandibular first molar regions were selected for hematoxylin and eosin staining, Masson's trichrome staining, picro-sirius red staining and immunohistochemistry analyses of transforming growth factor-β1 (TGF-β1), tissue inhibitor of metalloproteinase-1 (TIMP-1) and matrix metalloproteinase-1 (MMP-1). The gingival connective tissue area was measured and numbers of the TGF-β1-, TIMP-1- and MMP-1-positive cells were counted. The analysis of variance for factorial designs for testing the overall differences and Fisher least significant difference test for post hoc analysis were used to determine the significance levels. RESULTS: Cyclosporine A treatment led to overgrowth of gingival connective tissue in rats. In the cyclosporine A-treated rats, the expression of TGF-β1 and TIMP-1 was significantly upregulated, whereas expression of the MMP-1 was downregulated, along with thicker and denser collagen fibers. In rats treated with a combination of cyclosporine A and Tan IIA, the cyclosporine A-induced changes were alleviated. CONCLUSIONS: Cyclosporine A enhanced gingival fibrous overgrowth via upregulation of the TGF-β1 and TIMP-1 expression, and downregulation of MMP-1 expression. Tan IIA can effectively prevent cyclosporine A-induced gingival fibrous overgrowth in rats by downregulating TGF-β1 and TIMP-1 expression, and upregulating MMP-1 expression.
author list (cited authors)
Ma, S., Liu, W., Liu, P., Liu, J., Chen, L., & Qin, C.
complete list of authors
Ma, S||Liu, W||Liu, P||Liu, J||Chen, L||Qin, C