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    Please use this identifier to cite or link to this item: https://ir.csmu.edu.tw:8080/ir/handle/310902500/11273


    Title: The upregulation of transglutaminase-2 by cyclosporin a in human gingival fibroblasts is augmented by oxidative stress.
    Authors: Lee, SS
    Tsai, CH
    Kuan, YH
    Huang, FM
    Chang, YC
    Contributors: 中山醫學大學
    Date: 2013
    Issue Date: 2015-07-15T05:30:45Z (UTC)
    ISSN: 0022-3492
    Abstract: BACKGROUND:
    Transglutaminase-2 (TGM-2) has been implicated in several fibrotic disorders and can be induced by reactive oxygen species (ROS). Hence, the authors hypothesize that cyclosporin A (CsA) may regulate TGM-2 via ROS, and this regulation may have a role in the pathogenesis of CsA-induced gingival overgrowth.
    METHODS:
    Cytotoxicity, 2',7'-dichlorodihydrofluorescein diacetate assay, and Western blot were used to investigate the effects of CsA in human gingival fibroblasts (HGFs). In addition, extracellular signal-regulated kinase (ERK) inhibitor PD98059, phosphatidylinositol 3-kinase inhibitor LY294002, glutathione precursor N-acetyl-L-cysteine (NAC), curcumin, epigallocatechin-3 gallate (EGCG), and p38 inhibitor SB203580 were added to find the possible regulatory mechanisms.
    RESULTS:
    Concentrations of CsA >500 ng/mL demonstrated cytotoxicity to HGFs (P < 0.05). CsA enhanced the generation of intracellular ROS at concentrations >200 ng/mL (P <0.05). TGM-2 protein induced by CsA was found in HGFs in a dose- and time-dependent manner (P <0.05). The addition of PD98059, LY294002, NAC, curcumin, EGCG, and SB203580 markedly inhibited TGM-2 expression induced by CsA (P <0.05).
    CONCLUSIONS:
    These results demonstrate that CsA significantly upregulates intracellular ROS generation and elevates TGM-2 expression in HGFs. In addition, TGM-2 induced by CsA is downregulated by PD98059, LY294002, NAC, curcumin, EGCG, and SB203580.
    URI: https://ir.csmu.edu.tw:8080/ir/handle/310902500/11273
    http://dx.doi.org/10.1902/jop.2012.120554
    Relation: J Periodontol. 2013 Oct;84(10):1469-75.
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