title: Tanshinone IIA treatment alleviated the rat gingival connective tissue overgrowth induced by cyclosporine A.
abstract: 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.
  
  
  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.
authors.affiliation: Department of Periodontics, the First Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang, China.|Longjiang Scholar Laboratory, the First Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang, China.
authors.forename: S
authors.initials: S
authors.lastname: Ma
authors.affiliation: Department of Periodontics, the First Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang, China.
authors.forename: W
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Periodontics, the First Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang, China.
authors.forename: P
authors.initials: P
authors.lastname: Liu
authors.affiliation: Department of Periodontics, the First Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang, China.
authors.forename: J
authors.initials: J
authors.lastname: Liu
authors.affiliation: Longjiang Scholar Laboratory, the First Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang, China.
authors.forename: L
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Biomedical Sciences and Center for Craniofacial Research and Diagnosis, Texas, A&M University, Baylor College of Dentistry, Dallas, TX, USA.
authors.forename: C
authors.initials: C
authors.lastname: Qin
mesh_terms: D045784:Abietanes / Q000494:pharmacology*; D000818:Animals; D003238:Connective Tissue / Q000187:drug effects* / Q000473:pathology; D016572:Cyclosporine / Q000494:pharmacology*; D005881:Gingiva / Q000187:drug effects / Q000473:pathology; D019214:Gingival Overgrowth / Q000188:drug therapy*; D007150:Immunohistochemistry; D008297:Male; D008334:Mandible; D020781:Matrix Metalloproteinase 1 / Q000032:analysis / Q000378:metabolism; D008963:Molar; D051381:Rats; D017208:Rats, Wistar; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000032:analysis / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000032:analysis / Q000378:metabolism
chemical_list: D045784:Abietanes; D019715:Tissue Inhibitor of Metalloproteinase-1; D053773:Transforming Growth Factor beta1; C021751:tanshinone; D016572:Cyclosporine; D020781:Matrix Metalloproteinase 1
keywords: cyclosporine A; gingival overgrowth; matrix metalloproteinase-1; tanshinone IIA; tissue inhibitor of metalloproteinase-1; transforming growth factor-β1