Methyltransferase-like 3 leads to lung injury by up-regulation of interleukin 24 through N6-methyladenosine-dependent mRNA stability and translation efficiency in mice exposed to fine particulate matter 2.5

He, Xiang; Zhang, Lei; Liu, Shengbin; Wang, Junyi; Liu, Yao; Xiong, Anying; Jiang, Manling; Luo, Li; Xiong, Ying; Li, Guoping

doi:10.1016/j.envpol.2022.119607

Cited by 23 publications

(5 citation statements)

References 38 publications

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“…In the respiratory diseases, there are more and more literature reveal the important functions of m 6 A via variety of evidence ( Xu et al, 2022 ). For instance, m 6 A writer METTL3 is up-regulated in PM2.5 exposured mice lung injury and METTL3 up-regulated the m 6 A modification of Interleukin 24 (IL24) through via METTL3/YTHDF1-coupled epitranscriptomal regulation ( He et al, 2022 ). In lung ischemia/reperfusion injury, the m 6 A reader YTHDF3 or IGF2BP2 knockdown attenuates the hypoxia/reoxygenation-mediated inhibitory effects in BEAS-2B cells, as well as the hypoxia/reoxygenation-induced cell apoptosis ( Xiao et al, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

N⁶-methyladenosine reader YTHDF1 regulates the proliferation and migration of airway smooth muscle cells through m⁶A/cyclin D1 in asthma

Wang

Tian

et al. 2023

PeerJ

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Asthma is a chronic inflammatory respiratory disease, which is involved in multiple pathologic molecular mechanisms and presents a huge challenge to clinic nursing. Emerging evidence suggests that N6-methyladenosine (m6A) plays critical roles in respiratory system disease. Thus, present work tried to investigate the functions of m6A reader YTHDF 1 in asthma. The results indicated that YTHDF1 significantly upregulated in platelet-derived growth factor (PDGF) induced airway smooth muscle cells (ASMCs). Functionally, overexpression of YTHDF1 promoted the proliferation and migration of ASMCs, while YTHDF1 knockdown repressed the proliferation and migration. Mechanistically, there was a m6A modification site on cyclin D1 RNA (CCND1 genome) and YTHDF1 combined with cyclin D1 mRNA, thereby enhancing its mRNA stability via m6A-dependent manner. Collectively, these findings reveal a novel axis of YTHDF1/m6A/cyclin D1 in asthma’s airway remodeling, which may provide novel therapeutic strategy for asthma.

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Section: Discussionmentioning

confidence: 99%

N⁶-methyladenosine reader YTHDF1 regulates the proliferation and migration of airway smooth muscle cells through m⁶A/cyclin D1 in asthma

Wang

Tian

et al. 2023

PeerJ

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“…Additionally, we detected that METTL3 inhibition abrogates increased m6A methylation following LPS treatment and m6A demethylase inhibition increases endothelial permeability comparable to LPS. A few very recent studies supported this hypothesis that METTL3 contributed to PM2.5‐induced lung inflammation via IL‐24 upregulation, 97 and monocrotaline‐induced pulmonary hypertension via GLUT4 98 . This knowledge in addition to the literature that supports m6A RNA methylation's role in the development of several human diseases allowed us to hypothesize that METTL3 (as well as the METTL‐14‐WTAP complex) is a potential avenue for investigation of novel ALI therapies.…”

Section: Part III New Strategy For M6a Targeting Therapy Of Alimentioning

confidence: 91%

Exploring m6A‐RNA methylation as a potential therapeutic strategy for acute lung injury and acute respiratory distress syndrome

Faraj

Liang

et al. 2023

Pulm. circ.

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N6‐methyladenosine (m6A) is the most common methylation modification in mammalian messenger RNA (mRNA) and noncoding RNAs. m6A modification plays a role in the regulation of gene expression and deregulation of m6A methylation has been implicated in many human diseases. Recent publications suggest that exploitation of this methylation process may possess utility against acute lung injury (ALI). ALI and its more severe form, acute respiratory distress syndrome (ARDS) are acute, inflammatory clinical syndromes characterized by poor oxygenation and diffuse pulmonary infiltrates. This syndrome is associated with microvascular endothelial dysfunction, subsequent pulmonary hypertension and may ultimately lead to mortality without rigorous and acute clinical intervention. Over the years, many attempts have been made to detect novel therapeutic avenues for research without much success. The urgency for the discovery of novel therapeutic agents has become more pronounced recently given the current pandemic infection of coronavirus disease 2019 (COVID‐2019), still ongoing at the time that this review is being written. We review the current landscape of literature regarding ALI and ARDS etiology, pathophysiology, and therapeutics and present a potential role of m6A methylation. Additionally, we will establish the axiomatic principles of m6A methylation to provide a framework. In conclusion, METTL3, or methyltransferase‐like 3, the selective RNA methyltransferase for m6A, is a hub of proinflammatory gene expression regulation in ALI, and using a modern drug discovery strategy will identify new and effective ALI drug candidates targeting METTTL3.

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“…They were provided with ad libitum access to food and water and maintained under a 12-hour light-dark cycle to ensure optimal health and well-being. PM2.5-exposed model was prepared as our previously described [ 2 ]. Briefly, mice were exposed to PM2.5 (100 µg) via intranasal inhalation for continuous 14 days.…”

Section: Methodsmentioning

confidence: 99%

“…PM10 particles tend to accumulate in the nasal cavities and trachea. PM2.5 particles are small enough to evade airway cilia and mucociliary clearance, leading to direct entry into the bronchi and penetration deep into pulmonary alveoli [ 2 ]. Exposure to a 10 µg/m 3 increment in PM2.5 was associated with a 1.14% increase in the risk of all-cause mortality [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

Fine particulate matter 2.5 induces susceptibility to Pseudomonas aeruginosa infection via expansion of PD-L1high neutrophils in mice

Luo,

Jiang,

Xiong

et al. 2024

Respir Res

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Background Exposure to PM2.5 has been implicated in a range of detrimental health effects, particularly affecting the respiratory system. However, the precise underlying mechanisms remain elusive. Methods To address this objective, we collected ambient PM2.5 and administered intranasal challenges to mice, followed by single-cell RNA sequencing (scRNA-seq) to unravel the heterogeneity of neutrophils and unveil their gene expression profiles. Flow cytometry and immunofluorescence staining were subsequently conducted to validate the obtained results. Furthermore, we assessed the phagocytic potential of neutrophils upon PM2.5 exposure using gene analysis of phagocytosis signatures and bacterial uptake assays. Additionally, we utilized a mouse pneumonia model to evaluate the susceptibility of PM2.5-exposed mice to Pseudomonas aeruginosa infection. Results Our study revealed a significant increase in neutrophil recruitment within the lungs of PM2.5-exposed mice, with subclustering of neutrophils uncovering subsets with distinct gene expression profiles. Notably, exposure to PM2.5 was associated with an expansion of PD-L1high neutrophils, which exhibited impaired phagocytic function dependent upon PD-L1 expression. Furthermore, PM2.5 exposure was found to increase the susceptibility of mice to Pseudomonas aeruginosa, due in part to increased PD-L1 expression on neutrophils. Importantly, monoclonal antibody targeting of PD-L1 significantly reduced bacterial burden, dissemination, and lung inflammation in PM2.5-exposed mice upon Pseudomonas aeruginosa infection. Conclusions Our study suggests that PM2.5 exposure promotes expansion of PD-L1high neutrophils with impaired phagocytic function in mouse lungs, contributing to increased vulnerability to bacterial infection, and therefore targeting PD-L1 may be a therapeutic strategy for reducing the harmful effects of PM2.5 exposure on the immune system.

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Methyltransferase-like 3 leads to lung injury by up-regulation of interleukin 24 through N6-methyladenosine-dependent mRNA stability and translation efficiency in mice exposed to fine particulate matter 2.5

Cited by 23 publications

References 38 publications

N⁶-methyladenosine reader YTHDF1 regulates the proliferation and migration of airway smooth muscle cells through m⁶A/cyclin D1 in asthma

N⁶-methyladenosine reader YTHDF1 regulates the proliferation and migration of airway smooth muscle cells through m⁶A/cyclin D1 in asthma

Exploring m6A‐RNA methylation as a potential therapeutic strategy for acute lung injury and acute respiratory distress syndrome

Fine particulate matter 2.5 induces susceptibility to Pseudomonas aeruginosa infection via expansion of PD-L1high neutrophils in mice

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Methyltransferase-like 3 leads to lung injury by up-regulation of interleukin 24 through N6-methyladenosine-dependent mRNA stability and translation efficiency in mice exposed to fine particulate matter 2.5

Cited by 23 publications

References 38 publications

N6-methyladenosine reader YTHDF1 regulates the proliferation and migration of airway smooth muscle cells through m6A/cyclin D1 in asthma

N6-methyladenosine reader YTHDF1 regulates the proliferation and migration of airway smooth muscle cells through m6A/cyclin D1 in asthma

Exploring m6A‐RNA methylation as a potential therapeutic strategy for acute lung injury and acute respiratory distress syndrome

Fine particulate matter 2.5 induces susceptibility to Pseudomonas aeruginosa infection via expansion of PD-L1high neutrophils in mice

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N⁶-methyladenosine reader YTHDF1 regulates the proliferation and migration of airway smooth muscle cells through m⁶A/cyclin D1 in asthma

N⁶-methyladenosine reader YTHDF1 regulates the proliferation and migration of airway smooth muscle cells through m⁶A/cyclin D1 in asthma