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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 저널정보
- 대한치주과학회 Journal of Periodontal & Implant Science Journal of Periodontal & Implant Science 제47권 제2호
- 발행연도
- 2017.1
- 수록면
- 66 - 76 (11page)
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초록· 키워드
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Purpose: Oral wound healing requires gingival fibroblasts to respond to local growth factors. Epigenetic silencing through DNA methylation can potentially decrease the responsiveness of gingival fibroblasts to local growth factors. In this study, our aim was to determine whether the inhibition of DNA methylation sensitized gingival fibroblasts to transforming growth factor-β1 (TGF-β1).
Methods: Gingival fibroblasts were exposed to 5-aza-2'-deoxycytidine (5-aza), a clinically approved demethylating agent, before stimulation with TGF-β1. Gene expression changes were evaluated using quantitative polymerase chain reaction (PCR) analysis. DNA methylation was detected by methylation-sensitive restriction enzymes and PCR amplification.
Results: We found that 5-aza enhanced TGF-β1-induced interleukin-11 (IL11) expression in gingival fibroblasts 2.37-fold (P=0.008). 5-aza had no significant effects on the expression of proteoglycan 4 (PRG4) and NADPH oxidase 4 (NOX4). Consistent with this, 5-aza caused demethylation of the IL11 gene commonly next to a guanosine (CpG) island in gingival fibroblasts. The TGF-β type I receptor kinase inhibitor SB431542 impeded the changes in IL11 expression, indicating that the effects of 5-aza require TGF-β signaling. 5-aza moderately increased the expression of TGF-β type II receptor (1.40-fold; P=0.009), possibly enhancing the responsiveness of fibroblasts to TGF-β1. As part of the feedback response, 5-aza increased the expression of the DNA methyltransferases 1 (DNMT1) (P=0.005) and DNMT3B (P=0.002), which are enzymes responsible for gene methylation.
Conclusions: These in vitro data suggest that the inhibition of DNA methylation by 5-aza supports TGF-β-induced IL11 expression in gingival fibroblasts.
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참고문헌 (41)
참고문헌 신청
Xiao X / 2015 / Epigenetic repression of Krüppel-like factor 4 through Dnmt1 contributes to EMT in renal fibrosis / Int J Mol Med 35:1596~1602
Zhang Q / 2005 / Restoration of expression of transforming growth factor-beta type II receptor in murine renal cell carcinoma(renca)cells by 5-Aza-2'-deoxycytidine / Life Sci 76:1159~1166
Takai R / 2016 / DNA hypermethylation of extracellular matrix-related genes in human periodontal fibroblasts induced by stimulation for a prolonged period with lipopolysaccharide derived from Porphyromonas gingivalis / J Periodontal Res 51:508~517
Zhang S / 2013 / Epigenetic regulation of TNFA expression in periodontal disease / J Periodontol 84:1606~1616
Kojima A / 2016 / Tumor necrosis factor-alpha gene promoter methylation in Japanese adults with chronic periodontitis and rheumatoid arthritis / J Periodontal Res 51:350~358
Zhang Q / 2005 / Restoration of expression of transforming growth factor-beta type II receptor in murine renal cell carcinoma(renca)cells by 5-Aza-2'-deoxycytidine / Life Sci 76:1159~1166
Takai R / 2016 / DNA hypermethylation of extracellular matrix-related genes in human periodontal fibroblasts induced by stimulation for a prolonged period with lipopolysaccharide derived from Porphyromonas gingivalis / J Periodontal Res 51:508~517
Zhang S / 2013 / Epigenetic regulation of TNFA expression in periodontal disease / J Periodontol 84:1606~1616
Kojima A / 2016 / Tumor necrosis factor-alpha gene promoter methylation in Japanese adults with chronic periodontitis and rheumatoid arthritis / J Periodontal Res 51:350~358
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