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A potential role for the silent information regulator 2 homologue 1 ( SIRT 1) in periapical periodontitis
Author(s) -
Kudo H.,
Takeichi O.,
Hatori K.,
Makino K.,
Himi K.,
Ogiso B.
Publication year - 2018
Publication title -
international endodontic journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.988
H-Index - 119
eISSN - 1365-2591
pISSN - 0143-2885
DOI - 10.1111/iej.12894
Subject(s) - resveratrol , umbilical vein , regulator , angiogenesis , vascular endothelial growth factor , immunofluorescence , microbiology and biotechnology , periodontitis , lipopolysaccharide , ve cadherin , chemistry , vegf receptors , biology , andrology , cancer research , medicine , immunology , in vitro , pharmacology , endothelial stem cell , dentistry , biochemistry , gene , antibody
Aim To investigate the role played by silent information regulator 2 homologue 1 ( SIRT 1) during angiogenesis of periapical periodontitis. Methodology Periapical granulomas were subjected to dual‐colour immunofluorescence imaging and real‐time polymerase chain reactions assaying the expression levels of SIRT 1, vascular endothelial growth factor ( VEGF ) and VE ‐cadherin. The association between Ki‐67 and SIRT 1 expression was also examined. Human umbilical vein endothelial cells ( HUVEC s) were treated with a combination of lipopolysaccharide and resveratrol (a SIRT 1 activator) or sirtinol (a SIRT 1 inhibitor); and the levels of mRNA s encoding SIRT 1, VEGF and VE ‐cadherin were determined. HUVEC tube formation was assayed in the presence of resveratrol or sirtinol. The Mann–Whitney U ‐test or the Tukey–Kramer test was used for statistical analysis. Results Ki‐67‐expressing cells, including endothelial cells, lay adjacent to SIRT 1‐expressing cells in periapical granulomas. In addition, SIRT 1‐expressing cells were detected adjacent to VEGF ‐expressing cells and VEGF ‐ or VE ‐cadherin‐expressing endothelial cells. SIRT 1, VEGF and VE ‐cadherin mRNA expression levels in periapical granulomas were significantly higher ( P = 0.0054, 0.0090 and 0.0090, respectively) than those in healthy gingival tissues. HUVEC s treated with resveratrol exhibited significantly higher expression of mRNA s encoding SIRT 1, VEGF and VE ‐cadherin ( P = 0.0019, 0.00005 and 0.0045, respectively) compared with controls, but sirtinol inhibited such expression. Resveratrol caused HUVEC s to form tube‐like structures, whilst sirtinol inhibited this process. Conclusions These findings suggest that SIRT 1 may stimulate angiogenesis in periapical granulomas by triggering the proliferation of endothelial cells and inducing VEGF and VE ‐cadherin expression.