ArticleNature cell biology2021
E-type prostanoid receptor 4 drives resolution of intestinal inflammation by blocking epithelial necroptosis.
Article in Nature cell biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 46 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
46 citing papers in PubMed, 64 citations in OpenAlex.
- Gut microbiota in chronic inflammation: the interplay with lipid mediators.Gut microbes · 2026Review
- The update of prostaglandin E2 receptor subtype 4 (EP4) in inflammatory diseases.Genes & diseases · 2026Review
- The kinase domain of RIPK3 tunes its scaffolding functions.Cell death and differentiation · 2026Article
- Persistent prostaglandin E2 upregulation and hormonal multi-resistance: A hypothesis for long COVID.Biochemistry and biophysics reports · 2026Article
- Article
- A study on the mechanism of IGFBP-3 affecting autophagy to partially protect against inflammatory damage in inflammatory bowel disease.Journal of bioenergetics and biomembranes · 2026Article
- What we know about prostaglandin pathway dysfunction in chronic enteropathies: From endoscopy to molecular diagnosis.Journal of translational internal medicine · 2026Article
- Geniposide Alleviates Inflammatory Bowel Disease by Regulating Intestinal Flora and Arginine Metabolism and Inhibiting the NF-κB Pathway Through Targeting Anxa5.Mediators of inflammation · 2026Article
- Caspase 6 deficiency exacerbates inflammatory bowel disease via enterocyte necroptosis and bacterial translocation.Cell death discovery · 2025Article
- A loss-of-function human ADAR variant activates innate immune response and promotes bowel inflammation.Nature communications · 2025Article
- Article
- DJ-1 counteracts Caveolin-1-mediated necroptosis to inhibit epithelial barrier dysfunction in colitis.Cell death & disease · 2025Article
- Emerging role of small RNAs in inflammatory bowel disease and associated colorectal cancer (Review).International journal of molecular medicine · 2025Review
- Meeting report - Alpine desmosome disease meeting 2024: advances and emerging topics in desmosomes and related diseases.Journal of cell science · 2025Article
- Untargeted plasma metabolomics based on liquid chromatography-mass spectrometry for the analysis ofFrontiers in veterinary science · 2025Article
- Mechanism of cell death and its application in the repair of inflammatory bowel disease by mesenchymal stem cells.Frontiers in immunology · 2025Review
- Intestinal epithelial Gasdermin C is induced by IL-4R/STAT6 signaling but is dispensable for gut immune homeostasis.Scientific reports · 2024Article
- PTGER4 signaling regulates class IIa HDAC function and SPINK4 mRNA levels in rectal epithelial cells.Cell communication and signaling : CCS · 2024Article
- SPMs exert anti-inflammatory and pro-resolving effects through positive allosteric modulation of the prostaglandin EP4 receptor.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Effects of DNA methylation and its application in inflammatory bowel disease (Review).International journal of molecular medicine · 2024Review
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
24 authors at 8 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Inflammatory bowel diseases present with elevated levels of intestinal epithelial cell (IEC) death, which compromises the gut barrier, activating immune cells and triggering more IEC death. The endogenous signals that prevent IEC death and break this vicious cycle, allowing resolution of intestinal inflammation, remain largely unknown. Here we show that prostaglandin E2 signalling via the E-type prostanoid receptor 4 (EP4) on IECs represses epithelial necroptosis and induces resolution of colitis. We found that EP4 expression correlates with an improved IBD outcome and that EP4 activation induces a transcriptional signature consistent with resolution of intestinal inflammation. We further show that dysregulated necroptosis prevents resolution, and EP4 agonism suppresses necroptosis in human and mouse IECs. Mechanistically, EP4 signalling on IECs converges on receptor-interacting protein kinase 1 to suppress tumour necrosis factor-induced activation and membrane translocation of the necroptosis effector mixed-lineage kinase domain-like pseudokinase. In summary, our study indicates that EP4 promotes the resolution of colitis by suppressing IEC necroptosis.
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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.