FTO Deficiency Alleviates LPS-induced Acute Lung Injury by TXNIP/NLRP3-mediated Alveolar Epithelial Cell Pyroptosis

American Journal of Respiratory Cell and Molecular Biology, Journal Year: 2024, Volume and Issue: 70(5), P. 351 - 363

Published: Jan. 25, 2024

N6-methyladenosine (m6A) plays a role in various diseases, but it has rarely been reported acute lung injury (ALI). The fat mass and obesity-associated (FTO) protein can regulate mRNA metabolism by removing m6A residues. This study aimed to examine the mechanism of demethylase FTO lipopolysaccharide (LPS)-induced ALI. Lung epithelial knockout mice knockdown/overexpression A549 cell lines were constructed evaluate effects on Bioinformatics analysis series vivo vitro assays used regulation. Rescue conducted whether impact ALI depended TXNIP/NLRP3 pathway. In LPS-induced ALI, RNA modification levels upregulated, expression was downregulated. vivo, alleviated alveolar structure disorder, tissue oedema, pulmonary inflammation improved survival mice. vitro, knockdown reduced damage death induced LPS, while overexpression exacerbated death. Mechanistically, bioinformatics revealed that TXNIP downstream target FTO. deficiency mitigated pyroptosis via confirmed pathway significantly reversed inhibitor SRI-37330. Deficiency alleviates pathway-mediated pyroptosis, which might be novel therapeutic strategy for combating

Language: Английский

---

Personalized medicine using omics approaches in acute respiratory distress syndrome to identify biological phenotypes

Respiratory Research, Journal Year: 2022, Volume and Issue: 23(1)

Published: Nov. 19, 2022

Abstract In the last decade, research on acute respiratory distress syndrome (ARDS) has made considerable progress. However, ARDS remains a leading cause of mortality in intensive care unit. presents distinct subphenotypes with different clinical and biological features. The pathophysiologic mechanisms may contribute to variability partially explain why some pharmacologic therapies for have failed improve patient outcomes. Therefore, identifying heterogeneity might be key strategy finding effective treatments. Research involving studies biomarkers genomic, metabolomic, proteomic technologies is increasing. These new approaches, which are dedicated identification quantitative analysis components from matrixes, help differentiate between types damage predict outcome risk. Omics offer opportunity development diagnostic tools personalized therapy ARDS. This narrative review assesses recent evidence regarding genomics, proteomics, metabolomics research.

Language: Английский

---

The biological function of m6A methyltransferase KIAA1429 and its role in human disease

PeerJ, Journal Year: 2022, Volume and Issue: 10, P. e14334 - e14334

Published: Nov. 10, 2022

KIAA1429 is a major m6A methyltransferase, which plays important biological and pharmacological roles in both human cancer or non-cancer diseases. produce tumorigenic role various cancers through regulating DAPK3, ID2, GATA3, SMC1A, CDK1, SIRT1 other targets, promoting cell proliferation, migration, invasion, metastasis tumor growth . At the same time, also effective non-tumor diseases, such as reproductive system cardiovascular The potential regulatory mechanism of dependent on modification related to mRNA, lncRNA, circRNA miRNAs. In this review, we summarized current evidence diseases its prognostic target.

Language: Английский

---

N6‐methyladenosine methylation regulator RBM15 promotes the progression of diabetic nephropathy by regulating cell proliferation, inflammation, oxidative stress, and pyroptosis through activating the AGE‐RAGE pathway

Environmental Toxicology, Journal Year: 2023, Volume and Issue: 38(11), P. 2772 - 2782

Published: Aug. 8, 2023

Diabetic nephropathy (DN) is a major cause of end-stage renal disease throughout the world, and m6A modification plays critical role in progression DN. We aimed to find m6A-related genes their regulatory mechanisms DN.The expression levels four important (METTL16, RBM15, IGF2BP1, ALKBH5) were detected by quantitative real-time PCR (RT-qPCR). RBM15 was chosen its function explored. The downstream pathway screened transcriptome sequencing. AGE, inflammation, oxidative stress determined with enzyme-linked immunosorbent assay, AGE-RAGE pathway-related proteins Western blot (WB). Cell proliferation assessed counting Kit-8 (CCK-8). pyroptosis-related evaluated RT-qPCR or WB.METTL16 up regulated mouse model DN, which more significant. Silencing recovered cell proliferation, reduced inflammation factors, inhibited pyroptosis high glucose-induced HK-2 cells. Transcriptome sequencing suggested that might be RBM15. knockdown AGE level proteins. After silencing we found activating increased promoted stress, induced gene pyroptosis, thereby facilitating DN through activation pathway.

Language: Английский

---

Inhibition of METTL3 alleviated LPS-induced alveolar epithelial cell apoptosis and acute lung injury via restoring neprilysin expression

Life Sciences, Journal Year: 2023, Volume and Issue: 333, P. 122148 - 122148

Published: Oct. 5, 2023

Language: Английский

---

METTL Family in Healthy and Disease

Molecular Biomedicine, Journal Year: 2024, Volume and Issue: 5(1)

Published: Aug. 19, 2024

Abstract Transcription, RNA splicing, translation, and post-translational protein modification are fundamental processes of gene expression. Epigenetic modifications, such as DNA methylation, play a crucial role in regulating The methyltransferase-like (METTL) family, constituent the 7-β-strand (7BS) methyltransferase subfamily, is broadly distributed across cell nucleus, cytoplasm, mitochondria. Members METTL through their S-adenosyl methionine (SAM) binding domain, can transfer methyl groups to DNA, RNA, or proteins, thereby impacting replication, transcription, mRNA participate maintenance normal function promote disease development. This review primarily examines involvement family differentiation, mitochondrial function, its association with tumor formation, nervous system, cardiovascular diseases. Notably, intricately linked cellular particularly regulation translation factors. represent important molecules development associated patient immunity tolerance radiotherapy chemotherapy. Moreover, future research directions could include drugs antibodies targeting structural domains, utilizing nanomaterials carry miRNA corresponding mRNA. Additionally, precise mechanisms underlying interactions between factors remain be clarified.

Language: Английский

---

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

Pulmonary Circulation, Journal Year: 2023, Volume and Issue: 13(2)

Published: April 1, 2023

Abstract N 6 ‐methyladenosine (m6A) is the most common methylation modification in mammalian messenger RNA (mRNA) and noncoding RNAs. m6A plays a role regulation of gene expression deregulation has been implicated many human diseases. Recent publications suggest that exploitation this process may possess utility against acute lung injury (ALI). ALI its more severe form, respiratory distress syndrome (ARDS) are acute, inflammatory clinical syndromes characterized by poor oxygenation diffuse pulmonary infiltrates. This associated with microvascular endothelial dysfunction, subsequent hypertension ultimately lead to mortality without rigorous intervention. Over years, attempts have made detect novel therapeutic avenues for research much success. The urgency discovery agents become pronounced recently given current pandemic infection coronavirus disease 2019 (COVID‐2019), still ongoing at time review being written. We landscape literature regarding ARDS etiology, pathophysiology, therapeutics present potential methylation. Additionally, we will establish axiomatic principles provide framework. In conclusion, METTL3, or methyltransferase‐like 3, selective methyltransferase m6A, hub proinflammatory ALI, using modern drug strategy identify new effective candidates targeting METTTL3.

Language: Английский

---

RNA modifications in pulmonary diseases

MedComm, Journal Year: 2024, Volume and Issue: 5(5)

Published: May 1, 2024

Abstract Threatening public health, pulmonary disease (PD) encompasses diverse lung injuries like chronic obstructive PD, fibrosis, asthma, infections due to pathogen invasion, and fatal cancer. The crucial involvement of RNA epigenetic modifications in PD pathogenesis is underscored by robust evidence. These not only shape cell fates but also finely modulate the expression genes linked progression, suggesting their utility as biomarkers targets for therapeutic strategies. critical implicated PDs are summarized this review, including N 6 ‐methylation adenosine, 1 5‐methylcytosine, pseudouridine (5‐ribosyl uracil), 7‐methylguanosine, adenosine inosine editing, along with relevant regulatory mechanisms. By shedding light on pathology PDs, these summaries could spur identification new strategies, ultimately paving way early diagnosis treatment innovation.

Language: Английский

---

Role and regulators of N6-methyladenosine (m6A) RNA methylation in inflammatory subtypes of asthma: a comprehensive review

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: July 23, 2024

Asthma is a common chronic inflammatory disease of the lungs and airway, yet its subtypes potential pathogenesis have not been completely elucidated require further study. With advances in epigenetic development, methylation has emerged as new direction for identifying decoding occurrence subtype manifestations asthma. N 6 -methyladenosine (m A), an RNA modification occurring -position adenosine, prevalent observed eukaryotes. It exerts significant control over mRNA metabolism by regulating alternative splicing, stability, export, translation. The dynamic process m A plays crucial role asthma tightly regulated three types regulators: writers, readers, erasers. This article provides comprehensive review association between regulators asthma, such involvement cells related response. Furthermore, findings presented herein provide insights solid foundation research on biomarkers diagnosis development personalized treatment different particularly neutrophilic eosinophilic

Language: Английский

---

Understanding how methyltransferase-like 3 functions in lung diseases: From pathogenesis to clinical application

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 179, P. 117421 - 117421

Published: Sept. 6, 2024

Language: Английский

---