{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T16:54:20Z","timestamp":1775926460054,"version":"3.50.1"},"reference-count":35,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2013,10,1]],"date-time":"2013-10-01T00:00:00Z","timestamp":1380585600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Periodontology"],"published-print":{"date-parts":[[2013,10]]},"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> Transglutaminase\u20102 (TGM\u20102) 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\u20102 via ROS, and this regulation may have a role in the pathogenesis of CsA\u2010induced gingival overgrowth.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> Cytotoxicity, 2\u2032,7\u2032\u2010dichlorodihydrofluorescein diacetate assay, and Western blot were used to investigate the effects of CsA in human gingival fibroblasts (HGFs). In addition, extracellular signal\u2010regulated kinase (ERK) inhibitor PD98059, phosphatidylinositol 3\u2010kinase inhibitor LY294002, glutathione precursor N\u2010acetyl\u2010L\u2010cysteine (NAC), curcumin, epigallocatechin\u20103 gallate (EGCG), and p38 inhibitor SB203580 were added to find the possible regulatory mechanisms.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> Concentrations of CsA &gt;500 ng\/mL demonstrated cytotoxicity to HGFs (<jats:italic>P<\/jats:italic> &lt; 0.05). CsA enhanced the generation of intracellular ROS at concentrations &gt;200 ng\/mL (<jats:italic>P<\/jats:italic> &lt;0.05). TGM\u20102 protein induced by CsA was found in HGFs in a dose\u2010 and time\u2010dependent manner (<jats:italic>P<\/jats:italic> &lt;0.05). The addition of PD98059, LY294002, NAC, curcumin, EGCG, and SB203580 markedly inhibited TGM\u20102 expression induced by CsA (<jats:italic>P<\/jats:italic> &lt;0.05).<\/jats:p><jats:p><jats:bold>Conclusions:<\/jats:bold> These results demonstrate that CsA significantly upregulates intracellular ROS generation and elevates TGM\u20102 expression in HGFs. In addition, TGM\u20102 induced by CsA is downregulated by PD98059, LY294002, NAC, curcumin, EGCG, and SB203580.<\/jats:p>","DOI":"10.1902\/jop.2012.120554","type":"journal-article","created":{"date-parts":[[2012,11,23]],"date-time":"2012-11-23T08:23:25Z","timestamp":1353659005000},"page":"1469-1475","source":"Crossref","is-referenced-by-count":18,"title":["The Upregulation of Transglutaminase\u20102 by Cyclosporin A in Human Gingival Fibroblasts Is Augmented by Oxidative 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