Abstract:
BACKGROUND AND OBJECTIVE:Ciclosporin A (CsA)-induced gingival overgrowth is attributed to an exaggerated accumulation of extracellular matrix, which is mainly due to an increased expression of transforming growth factor-β1 (TGF-β1). Herein, the in vitro investigation of effects of overexpression of Smad7, a TGF-β1 signaling inhibitor, in the events associated with CsA-induced extracellular matrix accumulation was performed. MATERIAL AND METHODS:The effects of Smad7 were assessed by stable overexpression of Smad7 in fibroblasts from normal gingiva. Smad7-overexpressing cells and control cells were incubated with CsA, and synthesis of type I collagen, production and activity of MMP-2 and cellular proliferation were evaluated by ELISA, zymography, growth curve, bromodeoxyuridine incorporation assay and cell cycle analysis. The effects of CsA on cell viability and apoptosis of fibroblasts from normal gingiva were also evaluated. Western blot and immunofluorescence for phospho-Smad2 were performed to measure the activation of TGF-β1 signaling. RESULTS:Although the treatment with CsA stimulated TGF-β1 production in both control and Smad7-overexpressing fibroblasts, its signaling was markedly inhibited in Smad7-overexpressing cells, as revealed by low levels of phospho-Smad2. In Smad7-overexpressing cells, the effects of CsA on proliferation, synthesis of type I collagen and the production and activity of MMP-2 were significantly blocked. Smad7 overexpression blocked CsA-induced fibroblast proliferation via p27 regulation. Neither CsA nor Smad7 overexpression induced cell death. CONCLUSION:The data presented here confirm that TGF-β1 expression is related to the molecular events associated with CsA-induced gingival overgrowth and suggest that Smad7 overexpression is effective in blocking these events, including proliferation, type I collagen synthesis and MMP-2 activity.
journal_name
J Periodontal Resjournal_title
Journal of periodontal researchauthors
Sobral LM,Aseredo F,Agostini M,Bufalino A,Pereira MC,Graner E,Coletta RDdoi
10.1111/j.1600-0765.2011.01412.xsubject
Has Abstractpub_date
2012-04-01 00:00:00pages
149-58issue
2eissn
0022-3484issn
1600-0765journal_volume
47pub_type
杂志文章abstract::To investigate the effect of lipopolysaccharide (LPS) on phagocytic activity of collagen fibrils by periodontal fibroblasts, we studied rat molar gingival connective tissue and periodontal ligament under light and electron microscopy after topical application of LPS (5 mg/ml in physiological salt solution (PS)) on the...
journal_title:Journal of periodontal research
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journal_title:Journal of periodontal research
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journal_title:Journal of periodontal research
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doi:10.1111/j.1600-0765.1999.tb02233.x
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更新日期:2018-02-01 00:00:00
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pub_type: 杂志文章,随机对照试验
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更新日期:2017-02-01 00:00:00
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journal_title:Journal of periodontal research
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journal_title:Journal of periodontal research
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journal_title:Journal of periodontal research
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