Notch promotes DNMT-mediated hypermethylation of <i>Klotho</i> leads to COPD-related inflammation

Qiu, Jie; Zhang, Yanan; Zheng, Xin; Zhang, Peng; Ma, Gang; Tan, Hai

doi:10.1080/01902148.2018.1556749

Cited by 16 publications

(7 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…When healthy dental pulp cells are exposed to lPS, pro-inflammatory chemokines and cytokines, including il-6 and il-8, are released, thus triggering subsequent inflammatory events (2). DNA methylation is a major epigenetic regulator that can influence the transcriptional expression of pro-inflammatory cytokines in the initiation and development of the inflammatory response (15)(16)(17). However, very little research has sought to define the function of DNA demethylation in the development of the LPS-inflamed dental pulp.…”

Section: Discussionmentioning

confidence: 99%

“…The roles and functions of dna methylation patterns have attracted extensive attention, but there has been particular emphasis on their roles in the pathological processes of cancer (14). Only recently have studies begun to shed light on the contribution of dnMTs to the initiation and progression of inflammatory diseases (15). A study on inflamed peripheral blood mononuclear cells (PBMCs) showed that DNMT1 expression decreased after treatment with LPS; dnMT1 modulated the methylation level of gene promoters, thus mediating the transcription of pro-inflammatory cytokines, including il-6, il-8 and tumor necrosis factor-α (TnF-α) (16).…”

Section: Dna Methyltransferase Dnmt1 Inhibits Lipopolysaccharide-induced Inflammatory Response In Human Dental Pulp Cells Involving the Mmentioning

confidence: 99%

See 1 more Smart Citation

DNA methyltransferase DNMT1 inhibits lipopolysaccharide‑induced inflammatory response in human dental pulp cells involving the methylation changes of IL‑6 and TRAF6

Cai

Zhan

et al. 2019

Mol Med Report

View full text Add to dashboard Cite

dental pulp inflammation is a pathological process characterized by local lesions in dental pulp and the accumulation of inflammatory mediators. DNA methylation of cytosine residues is a key epigenetic modification that is essential for gene transcription, and plays pivotal roles in inflammatory reactions and immune responses. However, the function of cytosine dna methylation in the innate immune defense against the inflammation of dental pulp is poorly understood. To investigate the effect of DNA methylation in inflamed dental pulp upon innate immune responses, expression levels of the dna methyltransferases (dnMT1, dnMT3a and dnMT3b) in human dental pulp cells (hdPcs) after lipopolysaccharide (LPS) stimulation were evaluated by western blotting and reverse transcription-quantitative (RT-q) PCR. Only DNMT1 expression was decreased, while the transcription of inflammatory cytokines was increased. in the immune responses of lPS-induced hdPcs, the results of RT-qPCR and ELISA showed that DNMT1 knockdown promoted the production of the pro-inflammatory cytokines, interleukin (IL)-6 and IL-8. Western blotting demonstrated that DNMT1 knockdown increased the phosphorylation levels of iKKα/β and p38 in the nF-κB and MaPK signaling pathways, respectively. Furthermore, MeDIP and RT-qPCR analysis demonstrated that the 5-methylcytosine levels of the IL-6 and TnF receptor-associated factor 6 (TRAF6) promoters were significantly decreased in DNMT1-deficient hDPCs.Taken together, these results indicated that the expression of DNMT1 was decreased after LPS stimulation in hDPCs. dnMT1 depletion increased lPS-induced cytokine secretion, and activated nF-κB and MaPK signaling; these mechanisms may involve the decreased methylation levels of the IL-6 and TRAF6 gene promoters. This study emphasized the role of DNMT1-dependent DNA methylation on the inflammation of LPS-infected dental pulp and provides a new rationale for the investigation of the molecular mechanisms of inflamed dental pulps.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Dna Methyltransferase Dnmt1 Inhibits Lipopolysaccharide-induced Inflammatory Response In Human Dental Pulp Cells Involving the Mmentioning

confidence: 99%

DNA methyltransferase DNMT1 inhibits lipopolysaccharide‑induced inflammatory response in human dental pulp cells involving the methylation changes of IL‑6 and TRAF6

Cai

Zhan

et al. 2019

Mol Med Report

View full text Add to dashboard Cite

show abstract

“…Qiu et al reported that treatment with CSE could induce the expression of DNMT1 and DNMT3a in both MH-S and 16HBE cells. 31 Chronic restraint stress might induce the expression of DNMT3a in rat lung cells. 32 In this study, we demonstrated that the expression of DNMT3a was increased in CSE-treated iDCs and that the inhibition of DNMT3a could regulate iDC-mediated Th17 cell differentiation.…”

Section: Discussionmentioning

confidence: 99%

Cigarette smoke extract promotes DNA methyltransferase 3a expression in dendritic cells, inducing Th‐17/Treg imbalance via the c‐Jun/allograft inflammatory factor 1 axis

Huang

Zhou

Luo

et al. 2021

The Kaohsiung J of Med Scie

View full text Add to dashboard Cite

Chronic obstructive pulmonary disease (COPD) is a chronic respiratory disorder.Although numerous studies on COPD have been conducted, therapeutic strategies for COPD are limited, and its pathological mechanism is still unclear. The present study aimed to explore the role of DNA methyltransferase 3a (DNMT3a) in dendritic cells (DCs) and the possible role of the Th-17/Treg cell balance in COPD. Immature DCs (iDCs) were induced and cocultured with CD4 + T cells. An in vitro COPD model was established by treatment with cigarette smoke extract (CSE). DNMT3a or allograft inflammatory factor 1 (AIF1) and c-Jun N-terminal kinase (JNK) were inhibited and overexpressed, respectively, by transfection with sh-DNMT3a or sh-AIF1 and JNK overexpression plasmids. The 3-(4,5-cimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay was used to measure cell viability. The Th17/Treg cell ratio was determined by flow cytometry. The expression levels of DNMT3a, c-Jun and AIF1 were measured using RT-qPCR or western blotting. Chromatin immunoprecipitation (CHIP) was used to confirm the interaction between c-Jun and the AIF1 promoter region. CSE stimulation promoted the expression of DNMT3a, and AIF1, and the ratio of p-c-Jun/c-Jun in iDCs. Besides, the iDC-mediated differentiation of Th17 cells was in a dose-dependent manner. However, knockdown of DNMT3a or AIF1 reversed the above effects caused by CSE. Inhibition of c-Jun signaling by treatment with the JNK inhibitor SP600125 also suppressed the iDC-mediated differentiation of Th17 cells, which was promoted by CSE. CHIP analysis showed that c-Jun could bind to the promoter region of AIF1. DNMT3a could regulate the iDC-mediated Th17/Treg balance by regulating the c-Jun/AIF1 axis.

show abstract

“… Barnawi et al (2017) had found phagocytosis of apoptotic cells by alveolar macrophages in patients with COPD to be controlled by epigenetic regulation, and decrease of methylation to possibly be the cause of increased S1PR5 gene expression in alveolar macrophages and of the defect in COPD-related efferent cells. Notch-mediated hypermethylation of Klotho in alveolar macrophages and airway epithelial cells inhibited the expression of Klotho and promoted inflammatory response and apoptosis in COPD ( Qiu et al, 2018 ). Demethylation of NF-κ B-mediated pathway gene is related to the deterioration of COPD.…”

Section: Biomarker In Tracheal Epithelium and Lung Tissuementioning

confidence: 99%

DNA Methylation: A Potential Biomarker of Chronic Obstructive Pulmonary Disease

Tang

Huang

et al. 2020

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Chronic obstructive pulmonary disease (COPD) is a serious public health concern worldwide. By 2040, 4.41 million people are estimated to expire annually due to COPD. However, till date, it has remained difficult to alter the activity or progress of the disease through treatment. In order to address this issue, the best way would be to find biomarkers and new therapeutic targets for COPD. DNA methylation (DNAm) may be a potential biomarker for disease prevention, diagnosis, and prognosis, and its reversibility further makes it a potential drug design target in COPD. In this review, we aimed to explore the role of DNAm as biomarkers and disease mediators in different tissue samples from patients with COPD.

show abstract

Notch promotes DNMT-mediated hypermethylation of Klotho leads to COPD-related inflammation

Cited by 16 publications

References 41 publications

DNA methyltransferase DNMT1 inhibits lipopolysaccharide‑induced inflammatory response in human dental pulp cells involving the methylation changes of IL‑6 and TRAF6

DNA methyltransferase DNMT1 inhibits lipopolysaccharide‑induced inflammatory response in human dental pulp cells involving the methylation changes of IL‑6 and TRAF6

Cigarette smoke extract promotes DNA methyltransferase 3a expression in dendritic cells, inducing Th‐17/Treg imbalance via the c‐Jun/allograft inflammatory factor 1 axis

DNA Methylation: A Potential Biomarker of Chronic Obstructive Pulmonary Disease

Contact Info

Product

Resources

About