FTO O-GlcNAcylation induces inactive form Pyrin expression, which suppresses NLRP3 inflammasome activation during LPS stimulation DOI Creative Commons
Xiao‐Lian Zhang, Lu Zhang, Min Liu

и другие.

Research Square (Research Square), Год журнала: 2024, Номер unknown

Опубликована: Ноя. 25, 2024

Abstract The fat mass and obesity-associated protein (FTO), as a key RNA N6-methyladenosine (m6A) demethylase, has been recently highlighted in modulating inflammatory response. However, the role underlying mechanisms of FTO, especially FTO O-GlcNAcylation, LPS-induced inflammasome remain elusive. Here we uncover that undergoes O-GlcNAcylation specifically at Ser95 site. LPS-enhanced promotes TRIM21-mediated ubiquitination degradation, subsequently increasing m6A-modified Mefv (encoding Pyrin) expression macrophages. LPS stimulation or increases inactive form Pyrin can not cause Pyrin-ASC-Casp1 activation. competitively blocks NLRP3-ASC-Casp1 assembly activation through Pyrin-PYD domain, reduces gasdermin D (GSDMD) pyroptosis restrains TNF-α/IL-1β/IL-6 production. O-GlcNAcylation-deficiency knockdown aggravates S. Typhimurium sepsis dextran sulfate sodium (DSS)-induced bowel diseases (IBD). Our findings clarify there is regulatory network among m6A modification, acts negative regulator NLPR3-ASC-Casp1 inflammasome. plays an anti-inflammatory LPS-treated Enhancement may offer potential therapeutic strategy for combating endotoxin-induced NLRP3-mediated responses sepsis.

Язык: Английский

Pyroptosis in health and disease: mechanisms, regulation and clinical perspective DOI Creative Commons
Yifan Liu,

Renjie Pan,

Yuzhen Ouyang

и другие.

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Сен. 20, 2024

Язык: Английский

Процитировано

33
FTO alleviated ferroptosis in septic cardiomyopathy via mediating the m6A modification of BACH1 DOI

Hua Zeng,

Junmei Xu, Rui Wu

и другие.

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Год журнала: 2024, Номер 1870(7), С. 167307 - 167307

Опубликована: Июнь 17, 2024

Язык: Английский

Процитировано

7
Role of Lipopolysaccharides in the Inflammation and Pyroptosis of Alveolar Epithelial Cells in Acute Lung Injury and Acute Respiratory Distress Syndrome DOI Creative Commons
Xiao Li Shen,

Linglin He,

Wanru Cai

и другие.

Journal of Inflammation Research, Год журнала: 2024, Номер Volume 17, С. 5855 - 5869

Опубликована: Авг. 1, 2024

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) represent a spectrum of common critical conditions characterized by damage death alveolar epithelial cells (AECs). Pyroptosis is form programmed cell with inflammatory characteristics, activation pyroptosis markers has been observed in AECs patients ALI/ARDS. Lipopolysaccharides (LPS) possess strong pro-inflammatory effects are crucial pathological factor leading to ALI animals. In LPS-induced models, undergo pyroptosis. However, physiologically pathologically relevant concentrations LPS lead minor on AEC viability minimal induction cytokine release vitro do not induce classical Nevertheless, can enter the cytoplasm directly non-classical when assisted extracellular vesicles from bacteria, HMGB1, pathogens. this review, we have explored concerning inflammation, viability, pyroptosis, analyzing key factors that influence actions. Notably, highlight intricate response within framework ARDS, emphasizing variable Despite vitro, under specific conditions, presenting potential pathways for therapeutic intervention. Collectively, understanding these mechanisms development targeted treatments mitigate responses ALI/ARDS, thereby enhancing patient outcomes severe conditions.

Язык: Английский

Процитировано

4
Integrating bulk and single-cell RNA sequencing data: unveiling RNA methylation and autophagy-related signatures in chronic obstructive pulmonary disease patients DOI Creative Commons

Shi‐Xia Liao,

Lanying Zhang, Liang Shi

и другие.

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Фев. 1, 2025

Chronic Obstructive Pulmonary Disease (COPD) is a heterogeneous lung disease influenced by epigenetic modifications, particularly RNA methylation. Emerging evidence also suggests that autophagy plays crucial role in immune cell infiltration and implicated COPD progression. This study aimed to investigate key methylation regulators explore the roles of pathogenesis. We analyzed tissue-based bulk sequencing single-cell (scRNA-seq) datasets from non-COPD patients, sourced Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified between samples, protein–protein interaction networks constructed. Univariate logistic regression shared DEGs gene sets. Functional enrichment analyses, including Ontology (GO), set analysis (GSEA), variation (GSVA), performed. Weighted co-expression network (WGCNA) conducted. Integration with scRNA-seq data further elucidated changes composition, communication assessed interactions macrophages other cells. AddModuleScore quantified effects. Finally, mouse model was used validate expression critical (FTO IGF2BP2) via RT-qPCR flow cytometry. As revealed, we 13 methylation-related enriched translation processes. GSEA GSVA revealed significant these pathways. WGCNA pinpointed hub linking autophagy. Integrated demonstrated marked reduction COPD, FTO IGF2BP2 emerging as regulators. Macrophages elevated scores had increased In models, decreased validated. Taken together, this highlights relation pathways context COPD. genes, such IGF2BP2, which found have macrophages. These findings provide novel genetic insights into mechanisms suggest potential avenues for developing diagnostic therapeutic strategies.

Язык: Английский

Процитировано

0
Brazilin alleviates acute lung injury via inhibition of ferroptosis through the SIRT3/GPX4 pathway DOI

Yan Xiao-pei,

Li Xu, Qi Chang

и другие.

APOPTOSIS, Год журнала: 2024, Номер unknown

Опубликована: Дек. 25, 2024

Язык: Английский

Процитировано

3
Tamping Down the Fire: Taming Pyroptosis through RNA Methylation in Acute Lung Injury DOI

Kun Woo D Shin,

Robert B. Hamanaka

American Journal of Respiratory Cell and Molecular Biology, Год журнала: 2024, Номер 70(5), С. 331 - 333

Опубликована: Фев. 14, 2024

"Tamping Down the Fire: Taming Pyroptosis through RNA Methylation in Acute Lung Injury." American Journal of Respiratory Cell and Molecular Biology, 0(ja), pp.

Язык: Английский

Процитировано

0
Baicalein suppresses inflammation and attenuates acute lung injury by inhibiting glycolysis via HIF‑1α signaling DOI Creative Commons
Zhongyou Liu,

Xiaona Zheng,

Ning Li

и другие.

Molecular Medicine Reports, Год журнала: 2024, Номер 31(1)

Опубликована: Ноя. 5, 2024

Baicalein, a flavonoid monomer compound isolated from the dried root of traditional Chinese herb Scutellaria baicalensis, has several pharmacological activities, such as anti‑inflammatory, anti‑angiogenic, antitumor, antimicrobial and antiviral properties. Acute lung injury (ALI) is characterized by alveolar epithelium capillary endothelium, which results in decreased volume, compliance, ventilation/perfusion mismatch, intrapulmonary edema, edema even acute hypoxemic respiratory failure. The present study aimed to investigate effects baicalein on inflammation. Bioinformatics analysis using network pharmacology predicted that hypoxia inducible factor‑1α (HIF‑1α) glycolysis signaling pathways were involved mechanism underlying therapeutic baicalein. Further in vitro vivo experiments, immunohistochemistry, immunofluorescence PCR, verified could inhibit HIF‑1α signaling, thus suppressing glycolysis, improving inflammatory responses ALI. Taken together, suggested anti‑inflammatory treating ALI associated with its ability suppress via pathway.

Язык: Английский

Процитировано

0
FTO O-GlcNAcylation induces inactive form Pyrin expression, which suppresses NLRP3 inflammasome activation during LPS stimulation DOI Creative Commons
Xiao‐Lian Zhang, Lu Zhang, Min Liu

и другие.

Research Square (Research Square), Год журнала: 2024, Номер unknown

Опубликована: Ноя. 25, 2024

Abstract The fat mass and obesity-associated protein (FTO), as a key RNA N6-methyladenosine (m6A) demethylase, has been recently highlighted in modulating inflammatory response. However, the role underlying mechanisms of FTO, especially FTO O-GlcNAcylation, LPS-induced inflammasome remain elusive. Here we uncover that undergoes O-GlcNAcylation specifically at Ser95 site. LPS-enhanced promotes TRIM21-mediated ubiquitination degradation, subsequently increasing m6A-modified Mefv (encoding Pyrin) expression macrophages. LPS stimulation or increases inactive form Pyrin can not cause Pyrin-ASC-Casp1 activation. competitively blocks NLRP3-ASC-Casp1 assembly activation through Pyrin-PYD domain, reduces gasdermin D (GSDMD) pyroptosis restrains TNF-α/IL-1β/IL-6 production. O-GlcNAcylation-deficiency knockdown aggravates S. Typhimurium sepsis dextran sulfate sodium (DSS)-induced bowel diseases (IBD). Our findings clarify there is regulatory network among m6A modification, acts negative regulator NLPR3-ASC-Casp1 inflammasome. plays an anti-inflammatory LPS-treated Enhancement may offer potential therapeutic strategy for combating endotoxin-induced NLRP3-mediated responses sepsis.

Язык: Английский

Процитировано

0