MTHFD2 stabilizes LOX expression through RNA methylation modification to promote sepsis-induced acute kidney injury progression

Human Cell, Journal Year: 2025, Volume and Issue: 38(2)

Published: Feb. 26, 2025

Language: Английский

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Inhibition of Alkbh5 Attenuates Lipopolysaccharide‐Induced Lung Injury by Promoting Ccl1 m6A and Treg Recruitment

Cell Proliferation, Journal Year: 2025, Volume and Issue: unknown

Published: April 20, 2025

ABSTRACT This paper discussed the role of AlkB homologue 5 (Alkbh5) in progression lipopolysaccharide (LPS)‐induced acute lung injury (ALI). LPS‐induced ALI models were established Alkbh5 knockout (KO) and knock‐in (KI) mice. The m6A levels tissues analysed using dot assays. was by determining ALI‐related markers histological staining. Mouse MLE12 cells exposed to LPS for vitro experiments, influence on cell viability, apoptosis reactive oxygen species (ROS) production analysed. RNA‐seq analysis performed analyse gene changes upon deficiency. Functions Alkbh5‐C‐C motif chemokine ligand 1 (Ccl1) cascade further verified antagonist DDO‐2728 a recombinant protein Ccl1 (mCcl1). upregulated following exposure. mice mitigated injury, as indicated reduced serum immune infiltration, fibrosis apoptosis. Conversely, overexpression resulted reverse trends. In vitro, knockdown enhanced viability while reducing ROS production. Mechanistically, found bind destabilise mRNA, leading increased Treg recruitment. Treatment with or mCcl1 thus improving tissue pathology injury. study suggests that is implicated Ccl1‐mediated recruitment, making it promising target management.

Language: Английский

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METTL3-m6A methylation inhibits the proliferation and viability of type II alveolar epithelial cells in acute lung injury by enhancing the stability and translation efficiency of Pten mRNA

Respiratory Research, Journal Year: 2024, Volume and Issue: 25(1)

Published: July 15, 2024

Abstract Background The pathogenesis of acute lung injury (ALI) involves a severe inflammatory response, leading to significant morbidity and mortality. N6-methylation adenosine (m6A), an abundant mRNA nucleotide modification, plays crucial role in regulating metabolism function. However, the precise impact m6A modifications on progression ALI remains elusive. Methods models were induced by either intraperitoneal injection lipopolysaccharide (LPS) into C57BL/6 mice or LPS-treated alveolar type II epithelial cells (AECII) vitro. viability proliferation AECII assessed using CCK-8 EdU assays. whole-body plethysmography was used record general respiratory functions. M6A RNA methylation level after LPS insults detected, then “writer” screened. Afterwards, we successfully identified targets that underwent mediated METTL3, methyltransferase-like enzyme. Last, evaluated regulatory METTL3-medited at phosphatase tensin homolog ( Pten ) ALI, assessing proliferation, inflammation AECII. Results marked damages functions cellular injuries modification expression methyltransferase, exhibited notable rise both tissues cultured subjected treatment. METTL3 knockdown inhibition improved AECII, also reduced level. In addition, stability translation enhanced METTL3-mediated over-expression PTEN reversed protective effect Conclusions can be attributed elevated levels as it promotes through modification. This suggests targeting could offer novel approach for treating ALI.

Language: Английский

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Molecular mechanism of ALKBH5‐mediated m6A demethylation regulating lipopolysaccharide‐induced epithelial–mesenchymal transition in sepsis‐induced acute kidney injury

The Kaohsiung Journal of Medical Sciences, Journal Year: 2024, Volume and Issue: 40(11), P. 985 - 995

Published: Sept. 17, 2024

Abstract This study explored the mechanism by which m6A demethylase ALKBH5 mediates epithelial–mesenchymal transition (EMT) in sepsis‐associated acute kidney injury (SA‐AKI) and AKI‐chronic disease (CKD) transition. HK‐2 cells were stimulated with lipopolysaccharide (LPS) to establish an vitro model of SA‐AKI. expression was reduced through transfection si‐ALKBH5. Cell viability, apoptosis, migration detected CCK‐8 assay, TUNEL staining, Transwell. The levels TNF‐α, IL‐1β, IL‐6 measured enzyme‐linked immunosorbent assay. Quantitative real‐time polymerase chain reaction or Western blotting performed determine expressions ALKBH5, miR‐205‐5p, DDX5, E‐cadherin, α‐SMA. level quantitatively analyzed. pri‐miR‐205 bound DGCR8 m6A‐modified after intervention RNA immunoprecipitation. A dual‐luciferase assay confirmed binding between miR‐205‐5p DDX5. highly expressed LPS‐induced cells. Inhibition increased cell repressed EMT. modification level, thereby promoting increase eventually targeting DDX5 expression. Low overexpression partially abolished inhibitory effect silencing on In conclusion, represses removing upregulate expression, EMT AKI‐CKD

Language: Английский

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Post-translational modifications in sepsis-induced organ dysfunction: mechanisms and implications

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

Published: Aug. 21, 2024

As a grave and highly lethal clinical challenge, sepsis, along with its consequent multiorgan dysfunction, affects millions of people worldwide. Sepsis is complex syndrome caused by dysregulated host response to infection, leading fatal organ dysfunction. An increasing body evidence suggests that the pathogenesis sepsis both intricate rapid involves various cellular responses signal transductions mediated post-translational modifications (PTMs). Hence, comprehensive understanding mechanisms functions PTMs within regulatory networks imperative for pathological processes, diagnosis, progression, treatment sepsis. In this review, we provide an exhaustive summary relationship between sepsis-induced Furthermore, explored potential applications in offering forward-looking perspective on infectious diseases.

Language: Английский

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The Role of m6A Methylation Genes in Predicting Poor Prognosis in Sepsis: Identifying Key Biomarkers and Therapeutic Targets

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 18, 2024

Sepsis is one of the leading causes death among seriously ill patients worldwide, affecting more than 30 million people annually and accounting for 1–2% hospitalizations. By analyzing GEO data set, this study explored relationship between m6A methylation gene poor prognosis sepsis, aiming at early detection providing basis timely intervention, so as to improve survival rate patients. GSE54514 transcriptome were extracted from database 31 with sepsis 72 without death. Key genes screened by DEGs, LASSO RF algorithms, then METTL3, WTAP RBM15 further verified qRT-PCR. The constructed nomogram model showed high accuracy in predicting These three are mainly involved chemokine signaling pathway, differentiation monocytes T cells, phagocytosis immune cells. Through analysis infiltrations, identification subtype, ratio clinical samples, it was found that probability immunosuppression score subtype lower higher. Finally, through inhibition METTL3 mouse model, protective effect demonstrated spleen cell flow cytometry analysis, enzyme-linked immunosorbent assay (ELISA) HE staining. findings provide potential biomarkers targets precision diagnosis treatment.

Language: Английский

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The role of m6A methylation genes in predicting poor prognosis in sepsis: identifying key biomarkers and therapeutic targets

European journal of medical research, Journal Year: 2024, Volume and Issue: 29(1)

Published: Dec. 19, 2024

Sepsis is one of the leading causes death among seriously ill patients worldwide, affecting more than 30 million people annually and accounting for 1–2% hospitalizations. By analyzing gene expression omnibus (GEO) data set, our team explored relationship between m6A methylation poor prognosis sepsis. The purpose this present study to examine new detection markers with prognosis, provide theoretical basis timely intervention improve survival rate patients. First, GSE54514 transcriptome were extracted from GEO database 31 sepsis related 72 survivors. Key genes screened differentially expressed (DEGs), least absolute shrinkage selection operator (LSAAO) random forest (RF). And then, METTL3, WTAP RBM15 further verified by quantitative reverse transcription PCR (qRT-PCR). constructed nomogram model showed high accuracy in predicting death. These three are mainly involved chemokine signaling pathway, differentiation monocytes T cells, phagocytosis immune cells. analysis that a score subtype linked lower immunosuppression higher rates clinical samples, suggesting better responses outcomes these Finally, protective effect METTL3 was demonstrated mouse applied inhibitor, conducting cell flow cytometry analysis, enzyme-linked immunosorbent assay (ELISA) hematoxylin–eosin (HE) staining. In conclusion, findings potential biomarkers targets early precision diagnosis treatment.

Language: Английский

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Curcumin‐induced exosomal FTO from bone marrow stem cells alleviates sepsis‐associated acute kidney injury by modulating the m6A methylation of OXSR1

The Kaohsiung Journal of Medical Sciences, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 30, 2024

Curcumin and bone marrow stem cells (BMSCs)-derived exosomes are considered to be useful for the treatment of many human diseases, including sepsis-associated acute kidney injury (SA-AKI). However, role underlying molecular mechanism curcumin-loaded BMSCs-derived in progression SA-AKI remain unclear. Exosomes (BMSCs-EXO

Language: Английский

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