Epigenetic Regulation of Immune and Inflammatory Responses in Rheumatoid Arthritis

Abstract

PurposeRheumatoid arthritis (RA) is a disease associated with multiple factors. Epigenetics can affect gene expression without altering the DNA sequence. In this study, we aimed to comprehensively analyze epigenetic regulation in RA.MethodsUsing the Gene Expression Omnibus database, we identified a methylation chip, RNA-sequencing, and miRNA microarray for RA. First, we searched for DNA methylation, genes, and miRNAs associated with RA using differential analysis. Second, we determined the regulatory networks for RA-specific methylation, miRNA, and m6A using cross-analysis. Based on these three regulatory networks, we built a comprehensive epigenetic regulatory network and identified hub genes.ResultsUsing a differential analysis, we identified 16,852 differentially methylated sites, 4877 differentially expressed genes, and 32 differentially expressed miRNAs. The methylation-expression regulatory network was mainly associated with the PI3K-Akt and T-cell receptor signaling pathways. The miRNA expression regulatory network was mainly related to the MAPK and chemokine signaling pathways. M6A regulatory network was mainly associated with the MAPK signaling pathway. Additionally, five hub genes were identified in the epigenetic regulatory network: CHD3, SETD1B, FBXL19, SMARCA4, and SETD1A. Functional analysis revealed that these five genes were associated with immune cells and inflammatory responses.ConclusionWe constructed a comprehensive epigenetic network associated with RA and identified core regulatory genes. This study provides a new direction for future research on the epigenetic mechanisms of RA.

Identification of Genetic Predisposition to Sjögren’s Syndrome by Whole Exome Sequencing

“…Several lines of evidence associated with our identified enriched genes support this hypothesis. For example, the products of the four most enriched candidate genes, AQP1, ABL2, CHD3, and RELN, participate in inflammatory activation, cell adhesion and migration, wound healing, and organ regeneration [36][37][38][39][40][41]. In addition, they play important roles in the nervous system and are associated with central and periphery neuropathies [39,[42][43][44][45][46].…”

Investigation of DNA methylation in autoimmune diseases with genome-wide association analysis

“…PI3K-Akt signalling pathway regulates the cellular inflammatory response, and hypermethylated-low expression genes were enriched in this pathway, which showed DNA methylation may activate the pathway and aggravate RA. Hypomethylated-high expression genes were also found to be affecting the T-cell receptor pathway, resulting in the pathogenesis of RA [6]. The differentially methylated regions identified above shed new light on epigenetic treatments.…”

“…A recent study identified several differentially methylated genes and associated signaling pathways [6]. PI3K-Akt signalling pathway regulates the cellular inflammatory response, and hypermethylated-low expression genes were enriched in this pathway, which showed DNA methylation may activate the pathway and aggravate RA.…”

“…Rheumatoid arthritis (RA) is a common autoimmune disease that can cause long-term conditions such as pain, swelling, and stiffness in the bone. The specific causes of RA are unknown, but some factors such as smoking and unhealthy diets can increase the risk of developing the disease [6]. DNA methylation, the most extensively researched epigenetic phenomenon, may serve as a composite indicator of many environmental exposures, making it an appealing candidate for research into disorders like RA that involve both hereditary and environmental aspects [7].…”

Progress of Research on the Treatment of Seroma after Inguinal Hernia Repair by Chinese and Western Medicine

“…Millimeter wave (millimeter wave) is a kind of electromagnetic wave, its frequency band is not too precise definition, usually the wavelength of 1 ~ 10 mm, the frequency of 30 ~ 300 GHz electromagnetic wave is called millimeter wave, it is located in the wavelength range of microwave and far infrared wave overlap, both the characteristics of the two wave spectrum, the wavelength of the commonly used clinical treatment instrument is 8mm, the frequency of 37.5 GHz. Millimeter wave is a series of non-thermal biological effects caused by electromagnetic radiation to regulate cell metabolism, accelerate the repair of damaged tissues, effectively enhance microcirculation, improve blood perfusion, reduce edema in the operating area and relieve pain [51][52]. It has been used in the treatment of rheumatoid arthritis, knee pain, low back pain, headache and other painful conditions [52][53][54][55].…”