ArticleCell death discovery2022
YTHDF1 alleviates sepsis by upregulating WWP1 to induce NLRP3 ubiquitination and inhibit caspase-1-dependent pyroptosis.
Article in Cell death discovery, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
55 citing papers in PubMed, 1 synthesis or guideline pooled it, 73 citations in OpenAlex.
- A systematic review of protein post-translational modifications in sepsis.Molecular biology reports · 2025Pooled it
- Targeting Cathepsin B with p-coumaric acid rescues WWP1-dependent proteasomal degradation of NLRP3 in hyperuricemic nephropathy.Molecular medicine (Cambridge, Mass.) · 2026Article
- mRedox biology · 2026Review
- Targeting WWP1 ameliorates osteoarthritis by suppressing KLF15 ubiquitination to restore mtDNA and mitochondrial function.Molecular genetics and genomics : MGG · 2026Article
- YTHDF1 mediates KLF2/VSIG4 axis to regulate Kupffer cell polarization to alleviate sepsis-induced liver injury.Genes and immunity · 2026Article
- Epitranscriptomics, immunometabolism, and NETosis: unlocking novel mechanisms of traditional Chinese medicine in COPD.Frontiers in immunology · 2026Review
- Article
- Pyroptosis Regulated by N6-Methyladenosine Modification: Implications for Pyroptosis-Related Disease Therapy.Journal of innate immunity · 2026Review
- Mechanosensitive snoRNA-like circular RNA sno-circCNOT1 drives endothelial dysfunction and atherosclerosis.Theranostics · 2026Article
- Novel Therapeutic Targets of Endothelial Inflammation in Acute Lung Injury and Acute Respiratory Distress Syndrome.Journal of respiratory biology and translational medicine · 2026Article
- mFrontiers in immunology · 2026Review
- Mitochondria at the intersections of RNA modifications and metabolism reprogramming implications in cell death, tumor microenvironment, and immunotherapy.Journal of hematology & oncology · 2025Review
- Epitranscriptomic modifications in programmed cell death: mechanistic insights and implications for liver diseases.Cellular & molecular biology letters · 2025Review
- RNA Modifications in Health and Disease.MedComm · 2025Review
- Cell death signaling and immune regulation: new perspectives on targeted therapy for sepsis.Cellular & molecular biology letters · 2025Review
- Review
- Updated insights into the molecular networks for NLRP3 inflammasome activation.Cellular & molecular immunology · 2025Review
- GYY4137-induced p65 sulfhydration protects synovial macrophages against pyroptosis by improving mitochondrial function in osteoarthritis development.Journal of advanced research · 2025Article
- eIF3a function in immunity and protection against severe sepsis by regulating B cell quantity and function through mActa pharmaceutica Sinica. B · 2025Article
- Review
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pyroptosis is inflammation-associated caspase-1-dependent programmed cell death, which confers a crucial role in sepsis. The present study intends to investigate the regulatory network and function of the microarray-predicted YTHDF1 in caspase-1-dependent pyroptosis of sepsis. Peripheral blood of patients with sepsis was collected to determine WWP1 and YTHDF1 expression. An in vitro sepsis cell model was induced in RAW264.7 cells using lipopolysaccharide (LPS) and ATP and an in vivo septic mouse model by cecal ligation and perforation (CLP). After gain- and loss-of-function assays in vitro and in vivo, TNF-α and IL-1β levels and the cleavage of gasdermin-D (GSDMD) were detected by ELISA and Western blot assay, followed by determination of lactate dehydrogenase (LDH) activity. Immunoprecipitation and meRIP assay were performed to detect the ubiquitination of NLRP3 and the m6A modification of WWP1 mRNA. The binding of WWP1 to YTHDF1 was explored using RIP-RT-qPCR and dual luciferase gene reporter assay. It was noted that WWP1 and YTHDF1 were downregulated in clinical sepsis samples, LPS + ATP-treated RAW264.7 cells, and CLP-induced mice. The ubiquitination of NLRP3 was promoted after overexpression of WWP1. WWP1 translation could be promoted by YTHDF1. Then, WWP1 or YTHDF1 overexpression diminished LDH activity, NLRP3 inflammasomes and caspase-1-mediated cleavage of GSDMD in LPS + ATP-induced RAW264.7 cells. Overexpressed YTHDF1 restrained inflammatory response in CLP-induced mice. Collectively, the alleviatory effect of m6A reader protein YTHDF1 may be achieved through promotion of NLRP3 ubiquitination and inhibition of caspase-1-dependent pyroptosis by upregulating WWP1.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.