ArticleProceedings of the National Academy of Sciences of the United States of America2024
Excessive nucleic acid R-loops induce mitochondria-dependent epithelial cell necroptosis and drive spontaneous intestinal inflammation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
What it found
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Who cites it
38 citing papers in PubMed, 35 citations in OpenAlex.
- Histidine metabolic reprogramming drives oxidative stress induced mtDNA release to promote necroptosis and airway inflammation in severe asthma.Redox biology · 2026Article
- Uhrf1-Mediated PKM2 Degradation via Ubiquitination Alleviates Inflammation and Pyroptosis in Inflammatory Bowel Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- LncRNA DLX6-AS1 promotes necroptosis through PI3K/AKT/mTOR signaling pathway in myocardial ischemia/reperfusion injury mice.Scientific reports · 2026Article
- The role of non-coding RNAs in regulating R-loop dynamics in cancer: Mechanisms and therapeutic implications.Acta pharmaceutica Sinica. B · 2026Review
- Current Status of Intestinal Stem Cell Research: Mechanisms, Intestinal Diseases, and Organoid Development.Cells · 2026Review
- Integrated Necroptosis Within Programmed Cell Death in Traumatic Brain Injury.Molecular neurobiology · 2026Review
- PROTAC-mediated regulation of programmed cell death: From molecular mechanisms to therapeutic breakthroughs.Innovation (Cambridge (Mass.)) · 2026Review
- Targeting TARDBP to Restore Colonic Barrier Integrity in Ulcerative Colitis via NFATC1 mRNA Destabilization.The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology · 2026Article
- Helicobacter pylori eradication in the face of escalating anti-microbial resistance: Geographic heterogeneity and emerging treatment strategies.Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology · 2026Review
- An integrated anti-aging framework targeting NADRedox biology · 2026Review
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- TDP-43 pathology triggers neuroinflammation and cognitive impairment by inducing microglial necroptosis.EMBO molecular medicine · 2026Article
- [Veratric acid relieves oxidative stress and DSS-induced colitis in mice by activating the Nrf2/HO-1 signaling pathway].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2026Article
- Nicotinamide Mononucleotide Modulates Endothelin-1 via NR4A1 and Histone Modifications in Canine Intestinal Epithelial Cells.Animals : an open access journal from MDPI · 2026Article
- PXR ribosylation at E194 amplifies NAPQI in acetaminophen‒induced liver injury in mice, rescued by Schisandrin B.Acta pharmacologica Sinica · 2026Article
- Treatment of Inflammatory Bowel Disease with Drugs Targeting PANoptosis: A Comprehensive Review.Biomedicines · 2026Review
- Reduced R-loop abundance at proinflammatory loci: a shared epigenetic mechanism in inflammatory and metabolic diseases.Frontiers in cardiovascular medicine · 2026Article
- Research Prospects for Necroptosis in Inflammatory Diseases: A Bibliometric Analysis.Current medicinal chemistry · 2026Review
- Myeloid-derived suppressor cells modulation in the context of tumor microenvironment for gastric cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Review
Corrections and comments
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Authors and funding
24 authors at 8 institutions in 2 countries.
Funding
Abstract
Oxidative stress, which can be activated by a variety of environmental risk factors, has been implicated as an important pathogenic factor for inflammatory bowel disease (IBD). However, how oxidative stress drives IBD onset remains elusive. Here, we found that oxidative stress was strongly activated in inflamed tissues from both ulcerative colitis patients and Crohn's disease patients, and it caused nuclear-to-cytosolic TDP-43 transport and a reduction in the TDP-43 protein level. To investigate the function of TDP-43 in IBD, we inducibly deleted exons 2 to 3 of Tardbp (encoding Tdp-43) in mouse intestinal epithelium, which disrupted its nuclear localization and RNA-processing function. The deletion gave rise to spontaneous intestinal inflammation by inducing epithelial cell necroptosis. Suppression of the necroptotic pathway with deletion of Mlkl or the RIP1 inhibitor Nec-1 rescued colitis phenotypes. Mechanistically, disruption of nuclear TDP-43 caused excessive R-loop accumulation, which triggered DNA damage and genome instability and thereby induced PARP1 hyperactivation, leading to subsequent NAD
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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 Socratic graph.