NAT10 accelerates pulmonary fibrosis through N4-acetylated TGFB1-initiated epithelial-to-mesenchymal transition upon ambient fine particulate matter exposure

Wu, Shenshen; Yin, Liang; Han, Ke; Jiang, Bo; Meng, Qingtao; Aschner, Michael; Li, Xiaobo; Chen, Rui

doi:10.1016/j.envpol.2023.121149

Cited by 6 publications

(2 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Results revealed that NAT10 was notably induced in pulmonary epithelia, and enhanced the stability of TGF-β1. Depletion of NAT10 markedly protected against PM2.5 exposureinduced pulmonary EMT and brosis, whereas TGF-β1 restoration offset the protective in uences of NAT10 inhibition [34]. Nevertheless, the research on ac4C acetylation is unclear in myocardial bers.…”

Section: Discussionmentioning

confidence: 99%

NAT10-mediated RNA ac4C acetylation contributes to the myocardial infarction induced cardiac fibrosis

Li,

Yushanjiang,

Fang

et al. 2023

Preprint

View full text Add to dashboard Cite

Cardiac fibrosis is featured cardiac fibroblast activation and extracellular matrix accumulation. Ac4C acetylation is an important epigenetic regulation of RNAs that has been recently discovered, and it is solely carried out by NAT10, the exclusive enzyme used for the modification. However, the potential regulatory mechanisms of ac4C acetylation in myocardial fibrosis following myocardial infarction remain poorly understood. In our study, we activated fibroblasts in vitro using TGF-β1 (20 ng/mL), followed by establishing a myocardial infarction mouse model to evaluate the impact of NAT10 on collagen synthesis and cardiac fibroblast proliferation. We utilized a NAT10 inhibitor, Remodelin, to attenuate the acetylation capacity of NAT10. In the cardiac fibrosis tissues of chronic myocardial infarction mice and cultured cardiac fibroblasts in response to TGF-β1 treatment, there was an elevation in the levels of NAT10 expression. This increase facilitated proliferation, the accumulation of collagens, as well as fibroblast-to-myofibroblast transition. Through the administration of Remodelin, we effectively reduced cardiac fibrosis in myocardial infarction mice by inhibiting NAT10's ability to acetylate mRNA. Inhibition of NAT10 resulted in changes in the collagen-related gene expression and ac4C acetylation levels. Mechanistically, we identified that the inhibition of NAT10 mRNA ac4C modification activated caspase-3 and promoted cardiac fibroblast apoptosis. Therefore, the crucial involvement of NAT10-mediated ac4C acetylation is significant in the cardiac fibrosis progression, affording promising molecular targets for the treatment of fibrosis and relevant cardiac diseases.

show abstract

Section: Discussionmentioning

confidence: 99%

NAT10-mediated RNA ac4C acetylation contributes to the myocardial infarction induced cardiac fibrosis

Li,

Yushanjiang,

Fang

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…TGF-β, considered an important regulatory center in the IPF epithelial network, promotes the fibrotic process via multiple signaling pathways, including the Smad, MAPK, and ERK signaling pathways, as well as epigenetic alterations ( Ye and Hu, 2021 ). In this regard, PM 2.5 exposure increases N-acetyltransferase 10 (NAT10) levels, which catalyze TGFB1 N4-acetylcytidine (ac4C) modification, which enhances its stability and ultimately accelerates lung EMT and fibrosis ( Wu et al, 2023b ). Furthermore, chronic PM 2.5 exposure could not only directly trigger activation of pulmonary fibroblasts and EMT in BEAS-2B and in human pulmonary fibroblast (HFL-1), but also indirectly promote fibroblast phenotypic transformation by extracellular signals.…”

Section: Pm-induced Dna and Histone Modifications Within The Context ...mentioning

confidence: 99%

Epigenetic mechanisms of particulate matter exposure: air pollution and hazards on human health

Gavito-Covarrubias,

Ramírez-Díaz,

Guzmán-Linares

et al. 2024

Front. Genet.

View full text Add to dashboard Cite

Environmental pollution nowadays has not only a direct correlation with human health changes but a direct social impact. Epidemiological studies have evidenced the increased damage to human health on a daily basis because of damage to the ecological niche. Rapid urban growth and industrialized societies importantly compromise air quality, which can be assessed by a notable accumulation of air pollutants in both the gas and the particle phases. Of them, particulate matter (PM) represents a highly complex mixture of organic and inorganic compounds of the most variable size, composition, and origin. PM being one of the most complex environmental pollutants, its accumulation also varies in a temporal and spatial manner, which challenges current analytical techniques used to investigate PM interactions. Nevertheless, the characterization of the chemical composition of PM is a reliable indicator of the composition of the atmosphere, the quality of breathed air in urbanized societies, industrial zones and consequently gives support for pertinent measures to avoid serious health damage. Epigenomic damage is one of the most promising biological mechanisms of air pollution-derived carcinogenesis. Therefore, this review aims to highlight the implication of PM exposure in diverse molecular mechanisms driving human diseases by altered epigenetic regulation. The presented findings in the context of pan-organic cancer, fibrosis, neurodegeneration and metabolic diseases may provide valuable insights into the toxicity effects of PM components at the epigenomic level and may serve as biomarkers of early detection for novel targeted therapies.

show abstract

Emerging role of RNA acetylation modification ac4C in diseases: Current advances and future challenges

Luo

Cao

Chen

et al. 2023

Biochemical Pharmacology

View full text Add to dashboard Cite

NAT10 accelerates pulmonary fibrosis through N4-acetylated TGFB1-initiated epithelial-to-mesenchymal transition upon ambient fine particulate matter exposure

Cited by 6 publications

References 40 publications

NAT10-mediated RNA ac4C acetylation contributes to the myocardial infarction induced cardiac fibrosis

NAT10-mediated RNA ac4C acetylation contributes to the myocardial infarction induced cardiac fibrosis

Epigenetic mechanisms of particulate matter exposure: air pollution and hazards on human health

Emerging role of RNA acetylation modification ac4C in diseases: Current advances and future challenges

Contact Info

Product

Resources

About