Role of TLR9 methylation on its active transcription in apical inflammation

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dc.contributor.authorFernandez, Alejandra
dc.contributor.authorAstorga, Jessica
dc.contributor.authorJose Bordagaray, Maria
dc.contributor.authorJesus Lira, Maria
dc.contributor.authorGebicke-Haerter, Peter J.
dc.contributor.authorHernandez, Marcela
dc.date.accessioned2024-01-10T14:23:13Z
dc.date.available2024-01-10T14:23:13Z
dc.date.issued2022
dc.description.abstractAim To explore the methylation pattern, its role in transcriptional regulation and potential modifiers of methylation of the TLR9 gene in chronic periapical inflammation. Methodology In this cross-sectional study, apical lesions of endodontic origin (ALEO, n = 61) and healthy periodontal ligaments (HPL, n = 15) were included. Products from bisulfited and PCR-amplified DNA were analysed for their methylation profiles in the promoter region and at each CpG island. Additionally, TLR9 mRNA levels were quantified by qPCR and bivariate and multiple modelling were performed to better understand the influence of methylation on gene transcription. Results TLR9 mRNA levels were upregulated in ALEO compared to HPL (p < .001). TLR9 promoter CpG sites and CpG +2086 in the intragenic island 1 were demethylated in ALEO compared to HPL (p < .05). Multivariate analysis, adjusted by smoking and gender, revealed that demethylation of TLR9 promoter sites enhanced transcriptional activity, specifically demethylated CpGs at positions -736 and -683, (p = .02), which are close to CRE binding. Although ALEO reduced the global methylation of the gene promoter and intragenic-island 2 (p < .05) by -42.5 and -9.5 percentage points, respectively, age reduced the global methylation of intragenic-island 3 within the exon 2. Conclusions Demethylations of TLR9 promoter CpG sites, along with the intragenic DNA methylation status, were involved in higher transcription in ALEO. Hence, chronic periapical inflammation and ageing modify the methylation status both in the gene promoter and in intragenic CpG islands.
dc.description.funderFondo Nacional de Desarrollo Cientifico y Tecnologico (FONDECYT)
dc.fechaingreso.objetodigital2024-05-07
dc.fuente.origenWOS
dc.identifier.doi10.1111/iej.13745
dc.identifier.eissn1365-2591
dc.identifier.issn0143-2885
dc.identifier.urihttps://doi.org/10.1111/iej.13745
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/80063
dc.identifier.wosidWOS:000787778300001
dc.information.autorucFacultad de Medicina; Lira Salas, Maria Jesus; S/I; 195663
dc.issue.numero7
dc.language.isoen
dc.nota.accesocontenido parcial
dc.pagina.final794
dc.pagina.inicio784
dc.publisherWILEY
dc.rightsacceso restringido
dc.subjectCpG island
dc.subjectDNA methylation
dc.subjectinfection
dc.subjectperiapical periodontitis
dc.subjectRNA messenger
dc.subjecttoll-like receptor 9
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleRole of TLR9 methylation on its active transcription in apical inflammation
dc.typeartículo
dc.volumen55
sipa.codpersvinculados195663
sipa.indexWOS
sipa.trazabilidadCarga SIPA;09-01-2024
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