Regulation of N6-methyladenosine (m6A) RNA methylation in microglia-mediated inflammation and ischemic stroke

Zhang, Fangfang; Ran, Yuanyuan; Tahir, Muhammad Mobeen; Wang, Jianan; Chen, Xuechai

doi:10.3389/fncel.2022.955222

Cited by 16 publications

(6 citation statements)

References 136 publications

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“…[24][25][26][27] The expression of p38, ERK, and JNK is influenced by a variety of factors, with m6A RNA methylation being one of the most common post-transcriptional modifications documented in a variety of inflammatory diseases. 28 Consistent with our findings, m6A regulators may be involved in the inflammatory response induced by M1 macrophage hyperactivation by regulating the MAPK signaling pathway, thereby participating in the development of COPD. 10,29,30…”

Section: Discussionsupporting

confidence: 92%

The Activation of M1 Macrophages is Associated with the JNK-m6A-p38 Axis in Chronic Obstructive Pulmonary Disease

Hu,

Pang,

et al. 2023

COPD

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Background Excessive activation of M1 macrophages affects the chronic inflammatory response of the airways and leads to the development of chronic obstructive pulmonary disease (COPD). Therefore, it needs to be closely monitored and investigated. MAPK signaling pathway is involved in the activation of M1 macrophages, and N6-methyladenosine (m6A) is involved in the pathogenesis of COPD. However, it is unknown whether activation of the MAPK signaling pathway is mediated by m6A in M1 macrophages in COPD. Methods The GEO data were analyzed using bioinformatics techniques to assess the differences between COPD and healthy individuals in the levels of M1 macrophages, their secreted cytokines, and m6A regulators. The MAPK signaling pathway was significantly enriched in the list of differentially regulated genes between COPD and healthy individuals. We further analyzed the correlation between M1 macrophages, m6A, and the MAPK signaling pathway. Next, blood samples from COPD and healthy individuals were collected and analyzed by using flow cytometry, ELISA, and RT-PCR. Western blotting was performed using CSE-induced THP-1 cells. COPD and healthy mice were used for Me-RIP sequencing and flow cytometry experiments. Validation of the results of the above bioinformatics analysis by molecular biology experiments and sequencing techniques. Results We found that GEO data and blood specimens from COPD patients showed increased M1 macrophages, higher levels of IL-6 and TNF-α, and higher mRNA expression of key mediators of the MAPK signaling pathway (p38, ERK, and JNK). Western blotting showed increased expression of p38, ERK, and JNK in the CSE group. In contrast, the expression of m6A regulators was low. Also, M1 macrophages in COPD mice were hyperactivated and had reduced m6A modifications of p38, ERK, and JNK compared with control. Conclusion m6A may be involved in M1 macrophage hyperactivation by regulating the MAPK signaling pathway, thereby influencing the development of COPD.

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Section: Discussionsupporting

confidence: 92%

The Activation of M1 Macrophages is Associated with the JNK-m6A-p38 Axis in Chronic Obstructive Pulmonary Disease

Hu,

Pang,

et al. 2023

COPD

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“…Stroke-related neuroinflammation is a unique therapeutic target that contributes to the inhibition of secondary cell death and improves patient outcomes [ 135 ]. Microglia and infiltrated macrophages have been established to play important roles in the inflammatory processes postischemic stroke [ 136 ], which can be modulated by m 6 A regulators [ 137 ].…”

Section: The Roles Of M 6 a Modification In The Pa...mentioning

confidence: 99%

N-methyladenosine modification in ischemic stroke: Functions, regulation, and therapeutic potential

Han

2024

Heliyon

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“…Glial cells are the most abundant cells and induce several changes in pathological conditions such as inflammation, demyelination and disruption of BBB ( You et al, 2022 ). RNA m6A modification is observed to regulate microglia’s inflammatory processes ( Zhang F. et al, 2022 ). Studies suggest that METTL3 promotes lipopolysaccharide (LPS)-induced microglial inflammation by activating the TNF receptor associated factor 6 (TRAF6)-NF-κB pathway ( Wen et al, 2022 ) and improves neuronal apoptosis and microglial activation by inactivating MyD88/NF-κB pathway ( Chen Y. et al, 2022 ).…”

Section: Effect Of Rna M6a Methylationmentioning

confidence: 99%

m6A methylation: Critical roles in aging and neurological diseases

Fan

Chen

et al. 2023

Front. Mol. Neurosci.

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N6-methyladenosine (m6A) is the most abundant internal RNA modification in eukaryotic cells, which participates in the functional regulation of various biological processes. It regulates the expression of targeted genes by affecting RNA translocation, alternative splicing, maturation, stability, and degradation. As recent evidence shows, of all organs, brain has the highest abundance of m6A methylation of RNAs, which indicates its regulating role in central nervous system (CNS) development and the remodeling of the cerebrovascular system. Recent studies have shown that altered m6A levels are crucial in the aging process and the onset and progression of age-related diseases. Considering that the incidence of cerebrovascular and degenerative neurologic diseases increase with aging, the importance of m6A in neurological manifestations cannot be ignored. In this manuscript, we focus on the role of m6A methylation in aging and neurological manifestations, hoping to provide a new direction for the molecular mechanism and novel therapeutic targets.

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Regulation of N6-methyladenosine (m6A) RNA methylation in microglia-mediated inflammation and ischemic stroke

Cited by 16 publications

References 136 publications

The Activation of M1 Macrophages is Associated with the JNK-m6A-p38 Axis in Chronic Obstructive Pulmonary Disease

The Activation of M1 Macrophages is Associated with the JNK-m6A-p38 Axis in Chronic Obstructive Pulmonary Disease

N-methyladenosine modification in ischemic stroke: Functions, regulation, and therapeutic potential

m6A methylation: Critical roles in aging and neurological diseases

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