DNA methylation levels of SOCS1 and LINE-1 in oral epithelial cells from aggressive periodontitis patients

Baptista, N.B.; Portinho, Danielle; Casarin, Renato Corrêa Viana; Vale, Hugo Felipe do; Casati, Márcio Z.; Souza, Ana Paula de; Andia, Denise Carleto

doi:10.1016/j.archoralbio.2014.03.015

Cited by 21 publications

(29 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The present study extends pioneering research on epigenetics in periodontal research that has investigated methylation changes in the promoter regions of disease-relevant genes coding for extracellular matrix proteins [27], chemokines and cytokines [282930], and signaling molecules [3132]. The importance of this research is underscored by recent reviews on epigenetics in periodontal disease [3334].…”

Section: Introductionmentioning

confidence: 64%

Inhibitors of DNA methylation support TGF-β1-inducedIL11expression in gingival fibroblasts

Șufaru

Beikircher

Weinhäusel

et al. 2017

J Periodontal Implant Sci

View full text Add to dashboard Cite

PurposeOral 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).MethodsGingival 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.ResultsWe 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.ConclusionsThese in vitro data suggest that the inhibition of DNA methylation by 5-aza supports TGF-β-induced IL11 expression in gingival fibroblasts.

show abstract

Section: Introductionmentioning

confidence: 64%

Inhibitors of DNA methylation support TGF-β1-inducedIL11expression in gingival fibroblasts

Șufaru

Beikircher

Weinhäusel

et al. 2017

J Periodontal Implant Sci

View full text Add to dashboard Cite

show abstract

“…The present study extends pioneering research on epigenetics in periodontal research that has investigated methylation changes in the promoter regions of disease-relevant genes coding for extracellular matrix proteins [27], chemokines and cytokines [28][29][30], and signaling molecules [31,32]. The importance of this research is underscored by recent reviews on epigenetics in periodontal disease [33,34].…”

Section: Introductionmentioning

confidence: 71%

“…The foundation for this discussion involves detailed knowledge of the role of epigenetic changes in causing age-and disease-related compromised oral wound healing. At present, only limited knowledge has been accumulated on methylation changes in periodontal disease, although relevant results have been obtained regarding extracellular matrix proteins [27], chemokines and cytokines [28][29][30], and signaling molecules [31,32]. It is not evident that impaired periodontal regeneration is caused by an inappropriate fibroblast cell response to TGF-β1; however, if this is the case, could this reduction be caused by epigenetic mechanisms?…”

Section: Discussionmentioning

confidence: 97%

“…There is a demand for preclinical studies testing whether 5-aza can support periodontal regeneration following conventional scaling and root planning, and also following regenerative strategies based on local applications of recombinant growth factors and enamel matrix derivatives, particularly because the latter preparations exert a TGF-β-like activity [40]. Also of interest are investigations into the impact of periodontal disease on the methylation status of promoter regions regulating extracellular matrix molecules [29], chemokines and cytokines [30], and signaling molecules [31]. Moreover, the virulence factors of periodontal pathogens such as Porphyromonas gingivalis and Treponema denticola [27] cause epigenetic changes in periodontal cells.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Inhibitors of DNA methylation support TGF-β1-induced IL11 expression in gingival fibroblasts

Șufaru

Beikircher

Weinhäusel

et al. 2017

J Periodontal Implant Sci

View full text Add to dashboard Cite

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.

show abstract

“…Assim como várias citocinas, pode ter uma regulação aberrante originada por processos epigenômicos (BAPTISTA et al, 2014;YASMIN et al, 2015). A hipermetilação do SOCS1 mediada pela DNMT1 leva à redução de sua expressão, elevando a produção de citocinas pró-inflamatórias como o TNF-α e a IL-6 (CHENG et al, 2014).…”

Section: Cabeça E Pescoçounclassified

Existe associação entre doença periodontal e câncer? Análise investigativa clínica

Stuani¹

View full text Add to dashboard Cite

DNA methylation levels of SOCS1 and LINE-1 in oral epithelial cells from aggressive periodontitis patients

Cited by 21 publications

References 30 publications

Inhibitors of DNA methylation support TGF-β1-inducedIL11expression in gingival fibroblasts

Inhibitors of DNA methylation support TGF-β1-inducedIL11expression in gingival fibroblasts

Inhibitors of DNA methylation support TGF-β1-induced IL11 expression in gingival fibroblasts

Existe associação entre doença periodontal e câncer? Análise investigativa clínica

Contact Info

Product

Resources

About