Dataset Information

RFX1 downregulation contributes to TLR4 overexpression in CD14⁺ monocytes via epigenetic mechanisms in coronary artery disease.

ABSTRACT:

Background

Toll-like receptor 4 (TLR4) expression is increased in activated monocytes, which play a critical role in the pathogenesis of coronary artery disease (CAD). However, the mechanism remains unclear. Regulatory factor X1 (RFX1) is a critical transcription factor regulating epigenetic modifications. In this study, we investigated whether RFX1 and epigenetic modifications mediated by RFX1 contributed to the overexpression of TLR4 in activated monocytes.

Results

Compared with those of the controls, the mRNA and protein expression of RFX1 were downregulated and the mRNA expression of TLR4 was upregulated in CD14⁺ monocytes obtained from CAD patients and CD14⁺ monocytes obtained from healthy controls treated with low-density lipoprotein (LDL). The mRNA expression of RFX1 was negatively correlated with the mRNA expression of TLR4 in CD14⁺ monocytes. RFX1 knockdown led to the overexpression of TLR4 and the activation of CD14⁺ monocytes. In contrast, the overexpression of RFX1 inhibited TLR4 expression and the activation of CD14⁺ monocytes stimulated with LDL. Moreover, TLR4 was identified as a target gene of RFX1. The results indicated that RFX1 downregulation contributed to the decreased DNA methylation and histone H3 lysine 9 trimethylation and the increased H3 and H4 acetylation in the TLR4 promoter via the lack of recruitments of DNA methyltransferase 1 (DNMT1), histone deacetylase 1 (HDAC1), and histone-lysine N-methyltransferase SUV39H1 (SUV39H1), which were observed in CD14⁺ monocytes of CAD patients.

Conclusions

Our results show that RFX1 expression deficiency leads to the overexpression of TLR4 and the activation of CD14⁺ monocytes in CAD patients by regulating DNA methylation and histone modifications, which highlights the vital role of RFX1 in the pathogenesis of CAD.

SUBMITTER: Du P

PROVIDER: S-EPMC6413463 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Publications

RFX1 downregulation contributes to TLR4 overexpression in CD14<sup>+</sup> monocytes via epigenetic mechanisms in coronary artery disease.

Du Pei P Gao Keqin K Cao Yu Y Yang Shuang S Wang Yang Y Guo Ren R Zhao Ming M Jia Sujie S

Clinical epigenetics 20190311 1

<h4>Background</h4>Toll-like receptor 4 (TLR4) expression is increased in activated monocytes, which play a critical role in the pathogenesis of coronary artery disease (CAD). However, the mechanism remains unclear. Regulatory factor X1 (RFX1) is a critical transcription factor regulating epigenetic modifications. In this study, we investigated whether RFX1 and epigenetic modifications mediated by RFX1 contributed to the overexpression of TLR4 in activated monocytes.<h4>Results</h4>Compared with ...[more]

PMID: 30857550

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Dataset Information

RFX1 downregulation contributes to TLR4 overexpression in CD14⁺ monocytes via epigenetic mechanisms in coronary artery disease.

Background

Results

Conclusions

Publications

RFX1 downregulation contributes to TLR4 overexpression in CD14<sup>+</sup> monocytes via epigenetic mechanisms in coronary artery disease.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

RFX1 downregulation contributes to TLR4 overexpression in CD14+ monocytes via epigenetic mechanisms in coronary artery disease.

Background

Results

Conclusions

Publications

RFX1 downregulation contributes to TLR4 overexpression in CD14<sup>+</sup> monocytes via epigenetic mechanisms in coronary artery disease.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

RFX1 downregulation contributes to TLR4 overexpression in CD14⁺ monocytes via epigenetic mechanisms in coronary artery disease.