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Nrf-2 regulates cyclosporine-stimulated HO-1 expression in Gingiva
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نویسنده
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chin y.-t. ,liao y.-w. ,fu m.m.j. ,tu h.-p. ,shen e.-c. ,nieh s. ,shih k.-c. ,fu e.
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منبع
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journal of dental research - 2011 - دوره : 90 - شماره : 8 - صفحه:995 -1000
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چکیده
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Cyclosporine-a (csa) stimulates heme oxygenase-1 (ho-1) expression in the gingiva,but the regulation and the role of ho-1 in gingival overgrowth are not well-understood. ho-1 is regulated by several transcription factors,such as nuclear factor-κb (nf-κb) and nuclear factor erythroid-2-related factor 2 (nrf-2). the aim of this study was to examine the role of nrf-2 in the regulation of csa-stimulated ho-1 expression in human gingival fibroblasts. nrf-2 sirna (sinrf-2),nf-κb,kinase inhibitors,and sulforaphane (sfn) were used to examine the nuclear translocation of nrf-2 and expression of ho-1 and transforming growth factor-β1 (tgf-β1) in cells. treatment with sinrf-2,but not with an nf-κb inhibitor,reduced csa-stimulated ho-1 mrna expression. erk inhibition significantly decreased csa-stimulated nrf-2 nuclear translocation and ho-1 mrna expression. pre-treatment with sfn showed that ho-1 plays a role in attenuating csa-mediated tgf-β1 expressions. these findings suggest that csa-stimulated ho-1 expression is mediated through the activation of erk,and that nrf-2 plays a protective role against csa-induced gingival fibrosis by modulating collagen turnover-related genes. © 2011 international & american associations for dental research.
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کلیدواژه
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cyclosporine A; ERK; gingival fibroblast; HO-1; Nrf-2; TGF-β1
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آدرس
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graduate institute of life sciences,national defense medical center,taipei,taiwan,department of periodontology,school of dentistry,national defense medical center and tri-service general hospital,po box 90048-507,taipei, Taiwan, institutes of biochemistry and molecular biology,national yang-ming university,taipei, Taiwan, division of periodontology,department of oral medicine,infection and immunity,harvard school of dental medicine,boston,ma, United States, department of dental hygiene,china medical university,taichung, Taiwan, dental department,buddhist tzu chi general hospital,taipei branch,sindian,taipei county, Taiwan, department of pathology,national defense medical center and tri-service general hospital,taipei, Taiwan, division of endocrinology and metabolism,taipei-veteran general hospital,taipei, Taiwan, department of periodontology,school of dentistry,national defense medical center and tri-service general hospital,po box 90048-507,taipei, Taiwan
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Authors
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