Novel insights into the regulatory role of N6-methyladenosine methylation modified autophagy in sepsis DOI Creative Commons

Cheng-Fei Bi,

Jia Liu, Xiao Hu

et al.

Aging, Journal Year: 2023, Volume and Issue: unknown

Published: Dec. 18, 2023

Sepsis is defined as a life-threatening organ dysfunction caused by dysregulated host response to infection. It characterized high morbidity and mortality one of the major diseases that seriously hang over global human health. Autophagy crucial regulator in complicated pathophysiological processes sepsis. The activation autophagy known be great significance for protecting sepsis induced dysfunction. Recent research has demonstrated N6-methyladenosine (m6A) methylation well-known post-transcriptional RNA modification controls epigenetic gene expression well number biological In addition, m6A affects stability, export, splicing translation transcripts involved autophagic process. Although it been suggested regulates metabolic more frequently seen progression pathogenesis, underlying molecular mechanisms m6A-modified have not thoroughly elucidated. present article fills this gap providing an review its potential role development novel therapeutics.

Language: Английский

The effect of N6-methyladenosine (m6A) factors on the development of acute respiratory distress syndrome in the mouse model DOI Open Access

Liming Fei,

Gengyun Sun, Juan Sun

et al.

Bioengineered, Journal Year: 2022, Volume and Issue: 13(3), P. 7622 - 7634

Published: March 1, 2022

Acute respiratory distress syndrome (ARDS) can cause loss of alveolar-capillary membrane integrity and life-threatening immune responses. The underlying molecular mechanisms ARDS remain unclear. N6-methyladenosine (m6A)-RNA modification plays an important part in many biological processes. However, it is not clear whether alters RNA methylation lung tissue. We tried to investigate the changes m6A-RNA tissues lipopolysaccharide (LPS)-induced mice. Lung tissue samples were collected detect expression m6A factors through hematoxylin eosin (HE) staining, quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR), immunohistochemical analysis western blot. overall levels mouse detected by UPLC-UV-MS. HE staining showed that degree inflammatory response was more severe LPS-3 h group. mRNA YTHDF1, YTHDC1 IGFBP3 remarkably up-regulated at, respectively, 6, 6 12 after LPS treatment. METTL16, FTO, METTL3, KIAA1429, RBM15, ALKBH5, YTHDF2, YTHDF3, YTHDC2 IGFBP2 significantly down-regulated at 24 protein METTL16 FTO increased, YTHDC1, YTHDF1 YTHDF3 a down-regulation trend induction. Overall increased In mice, LPS-induced may be involved regulation play roles occurrence development It suggested promising therapeutic target for ARDS.

Language: Английский

Citations

32
METTL3-Mediated N6-Methyladenosine Modification of Trim59 mRNA Protects Against Sepsis-Induced Acute Respiratory Distress Syndrome DOI Creative Commons
Yi Chen, Yuling Wu,

Linjie Zhu

et al.

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: May 25, 2022

N6-methyladenosine (m6A) RNA modification is a fundamental determinant of mRNA metabolism in eukaryotic cells and involved numerous physiological pathological processes. However, the specific role m6A sepsis-induced acute respiratory distress syndrome(ARDS) remains unknown. Here, we show that levels were significantly decreased septic lungs METTL3 was main regulator absence modification. Pulmonary endothelial barrier damage critical process pathogenesis lung injury during sepsis. regulated dysfunction inflammatory responses ARDS vivo vitro. Furthermore, identified tripartite motif-containing (Trim)59 as key effector Trim59 deficiency exacerbated injury. Mechanistically, inhibited through Trim59-associated NF-κB inactivation. Our findings revealed novel insights into epitranscriptional mechanisms via modifications, which has important application value diagnosis, prognosis, molecular-targeted therapy sepsis-associated

Language: Английский

Citations

29
FTO alleviated ferroptosis in septic cardiomyopathy via mediating the m6A modification of BACH1 DOI

Hua Zeng,

Junmei Xu, Rui Wu

et al.

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Journal Year: 2024, Volume and Issue: 1870(7), P. 167307 - 167307

Published: June 17, 2024

Language: Английский

Citations

7
Pulsatile Flow Increases METTL14-induced m6A modification and attenuates septic cardiomyopathy: an experimental study DOI Creative Commons
Shenyu Zhu, Kai Wang, Zhexuan Yu

et al.

International Journal of Surgery, Journal Year: 2024, Volume and Issue: unknown

Published: March 28, 2024

Introduction: Septic cardiomyopathy is a sepsis-mediated cardiovascular complication with severe microcirculatory malperfusion. Emerging evidence has highlighted the protective effects of pulsatile flow in case disturbance, yet underlying mechanisms are still elusive. The objective this study was to investigate N6-methyladenosine (m 6 A) modification alleviation septic associated extracorporeal membrane oxygenation (ECMO)-generated flow. Methods: Rat model established and supported under ECMO either or non-pulsatile Peripheral perfusion index (PPI) cardiac function parameters were measured using ultrasonography. Dot blot assay applied examine m A level, while qRT-PCR, Western blot, immunofluorescence, immunohistochemistry used measure expressions related genes. RNA immunoprecipitation performed validate interaction between molecules. Results: ECMO-generated significantly elevates PPI, improves myocardial function, protects endothelium, prolongs survival rat models cardiomyopathy. mediates METTL14-mediated zonula occludens- (ZO-) 1 mRNA which stabilizes ZO-1 depending on presence YTHDF2. suppresses PI3K-Akt signaling pathway, downstream molecule Foxo1, negative transcription factor METTL14, binds METTL14 promoter inhibits METTL14-induced modification. Conclusion: increases attenuates progression cardiomyopathy, suggesting that pulsatility might be new therapeutic strategy by alleviating disturbance.

Language: Английский

Citations

6
N6-methyladenosine (m6A) reader IGF2BP2 promotes gastric cancer progression via targeting SIRT1 DOI Open Access
Zili Zhang,

Yu Xing,

Wenqing Gao

et al.

Bioengineered, Journal Year: 2022, Volume and Issue: 13(5), P. 11541 - 11550

Published: May 2, 2022

N6-methyladenosine (m6A) modification acts as the most prevalent internal in eukaryotic mRNA. Emerging evidence shows critical biological roles of m6A key enzymes human cancers. However, binding protein IGF2BP2 gastric cancer (GC) progression are still unclear. In this study, we confirmed that was highly expressed GC cell lines and tumor tissues. Knocking down suppressed proliferation migration, repressed xenograft growth vivo, while overexpression promoted migration. Mechanistically, identified regulated proliferation/migration through recognizing sites SIRT1 general, our findings demonstrated a novel regulatory mechanism IGF2BP2/SIRT1 axis modulated an m6A-dependent manner, suggesting may be therapeutic target for GC.

Language: Английский

Citations

20
SILENCING M6A READER YTHDC1 REDUCES INFLAMMATORY RESPONSE IN SEPSIS-INDUCED CARDIOMYOPATHY BY INHIBITING SERPINA3N EXPRESSION DOI
Wenjing Xie, Anqi Zhang,

Xuliang Huang

et al.

Shock, Journal Year: 2023, Volume and Issue: 59(5), P. 791 - 802

Published: March 6, 2023

ABSTRACT Sepsis-induced cardiomyopathy (SIC) is one of the most common complications infection-induced sepsis. An imbalance in inflammatory mediators main factor leading to SIC . N 6 -methyladenosine (m A) closely related occurrence and development reader YTH domain containing 1 (YTHDC1) an m A recognition protein. However, role YTHDC1 remains unclear. Herein, we demonstrated that YTHDC1-shRNA inhibits inflammation, reduces mediators, improves cardiac function a LPS-induced mouse model. Based on Gene Expression Omnibus database analysis, serine protease inhibitor A3N differential gene SIC. Furthermore, RNA immunoprecipitation indicated (SERPINA3N) mRNA can bind YTHDC1, which regulates expression SERPINA3N. Serine A3N–siRNA reduced inflammation myocytes. In conclusion, SERPINA3N mediate levels Such findings add relationship between SIC, providing new research avenue for therapeutic mechanism

Language: Английский

Citations

12
MicroRNAs as regulators of cardiac dysfunction in sepsis: pathogenesis and diagnostic potential DOI Creative Commons
Zhen Liu, Feiyang Li,

Ningcen Li

et al.

Frontiers in Cardiovascular Medicine, Journal Year: 2025, Volume and Issue: 12

Published: Feb. 18, 2025

Sepsis, a life-threatening condition arising from an uncontrolled immune response to infection, can lead organ dysfunction, with severe inflammation potentially causing multiple failures. Sepsis-induced cardiac dysfunction (SIMD) is common and complication of sepsis, significantly increasing patient mortality. Understanding the pathogenesis SIMD crucial for improving treatment, microRNAs (miRNAs) have emerged as important regulators in this process. A comprehensive literature search was conducted PubMed, Science Direct, Embase databases up September 2024. The terms included ["miRNA" or "microRNA"] ["Cardiac" "Heart"] ["Sepsis" "Septic"], language limited English. After initial filtering by database engine, Excel software used further screen references. Duplicate articles, those without abstracts full texts, review/meta-analyses non-English articles were excluded. Finally, 106 relevant research data extraction analysis. complex involves mitochondrial oxidative stress, cardiomyocyte apoptosis pyroptosis, dysregulation myocardial calcium homeostasis, inhibitory factors, autonomic nervous regulation disorders, hemodynamic changes, structural alterations. miRNAs play diverse roles SIMD. They are involved regulating above-mentioned pathological processes. Although significant progress has been made understanding role SIMD, there still challenges. Some studies on limitations such small sample sizes failure account confounding factors. Research also faces issues like inconsistent measurement techniques unclear miRNA-target gene relationships. Moreover, translation miRNA-based into clinical applications hindered problems related miRNA stability, delivery mechanisms, off-target effects, long-term safety. In conclusion, potential diagnostic biomarkers. Further needed overcome existing challenges fully exploit diagnosis treatment

Language: Английский

Citations

0
Electroacupuncture pre-treatment exerts a protective effect on LPS-induced cardiomyopathy in mice through the delivery of miR-381 via exosomes DOI
Yong Chen,

Shuangli Chen,

Jingyu Zhang

et al.

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Journal Year: 2024, Volume and Issue: 1870(5), P. 167208 - 167208

Published: May 1, 2024

Language: Английский

Citations

3
Diagnostic, clustering, and immune cell infiltration analysis of m6A regulators in patients with sepsis DOI Creative Commons
Fenghui Li, Yuan Zhang, Zhiyun Peng

et al.

Scientific Reports, Journal Year: 2023, Volume and Issue: 13(1)

Published: Feb. 13, 2023

Abstract RNA N6-methladenosine (m6A) regulators are required for a variety of biological processes, including immune responses, and increasing evidence indicates that their dysregulation is closely associated with many diseases. However, the potential roles m6A in sepsis remain unknown. We comprehensively analyzed transcriptional variations interactions 26 based on Gene Expression Omnibus (GEO) database. A random forest (RF) model nomogram were established to predict occurrence risk patients. Then, two different subtypes defined by consensus clustering analysis, we explored correlation between cells. found 17 significantly differentially expressed patients without sepsis, strong correlations among these revealed. Compared support vector machine (SVM) model, RF had better predictive ability, therefore was used construct reliable containing 10 candidate In addition, algorithm identify m6A, which helped us distinguish levels cell infiltration inflammation sepsis. Comprehensive analysis revealed occurrence, This study may contribute development follow-up treatment strategies

Language: Английский

Citations

8
METTL3 achieves lipopolysaccharide-induced myocardial injury via m6A-dependent stabilization of Myh3 mRNA DOI Creative Commons
Chengwu Gong,

Jinlong Wu,

Hao Li

et al.

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Journal Year: 2023, Volume and Issue: 1870(7), P. 119503 - 119503

Published: May 27, 2023

Language: Английский

Citations

7