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Nifedipine induces periostin expression in gingival fibroblasts through TGF-beta
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نویسنده
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kim s.s. ,jackson-boeters l. ,darling m.r. ,rieder m.j. ,hamilton d.w.
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منبع
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journal of dental research - 2013 - دوره : 92 - شماره : 11 - صفحه:1022 -1028
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چکیده
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Gingival enlargement is a fibrotic condition that can arise from systemic administration of the dihydropyridine calcium channel blocker nifedipine. periostin,a transforming growth factor-beta (tgf-β)-inducible matricellular protein,has been associated with fibrosis in numerous tissues,but its expression has never been examined in nifedipine-influenced gingival enlargement (nige). the objective of this study was to assess if periostin up-regulation is associated with nige and whether nifedipine induces periostin expression in gingival fibroblasts. in nige tissue (n = 6),periostin is overexpressed in the gingival connective tissue compared with healthy control tissue (n = 6). the transcription factor p-smad2/3,which is associated with canonical tgf-β signaling,localizes to the nuclei in both hgfs and oral epithelial cells in nige tissues,but not in control healthy tissue. in vitro culture of hgfs with 30 and 100 ng/ml of nifedipine significantly increased periostin mrna and protein levels,which correlated with increased levels of active tgf-β and increased phosphorylation and nuclear localization of smad3. blocking of canonical tgf-β signaling through inhibition of the tgf-β receptor i with sb431542 significantly reduced nifedipine-induced smad3 phosphorylation and periostin expression. our results demonstrate that nifedipine up-regulates periostin in hgfs in a tgf-β-dependent manner. © international & american associations for dental research.
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کلیدواژه
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adverse drug reaction; dihydropyridine; fibrosis; gingival overgrowth; matricellular protein; SMAD3
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آدرس
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department of anatomy and cell biology,children's health research institute,london,on, Canada, department of pathology,children's health research institute,london,on, Canada, department of pathology,children's health research institute,london,on, Canada, department of physiology and pharmacology,children's health research institute,london,on,canada,department of paediatrics,children's health research institute,london,on, Canada, department of anatomy and cell biology,children's health research institute,london,on,canada,division of oral biology,schulich school of medicine and dentistry,university of western ontario,london,on, Canada
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Authors
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