ArticleJournal of immunology (Baltimore, Md. : 1950)2013
A critical role for TLR4 induction of autophagy in the regulation of enterocyte migration and the pathogenesis of necrotizing enterocolitis.
Article in Journal of immunology (Baltimore, Md. : 1950), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 100 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
100 citing papers in PubMed, 1 synthesis or guideline pooled it, 141 citations in OpenAlex.
- Enteral Feeding Interventions in the Prevention of Necrotizing Enterocolitis: A Systematic Review of Experimental and Clinical Studies.Nutrients · 2021Pooled it
- The central function and specific molecular mechanisms of the TLR4 pathway underlying impaired intestinal barrier in necrotizing enterocolitis.Biochemistry and biophysics reports · 2026Review
- Blockade of NKp46⁻ CCR6⁻ ILC3 autophagy protects against necrotizing enterocolitis by restoring energy metabolism balance in mice.Nature communications · 2026Article
- Necrotizing enterocolitis.Nature reviews. Disease primers · 2026Review
- Murine intestinal epithelial cells and lymphocytes undergo contrasting inflammatory shifts during gastrointestinal development.Pediatric research · 2026Article
- Pathogenesis of necrotizing enterocolitis: mechanisms and mediators.World journal of pediatric surgery · 2026Review
- Digging deeper into necrotizing enterocolitis: bridging clinical, microbial, and molecular perspectives.Gut microbes · 2025Review
- The microbiome's hidden influence: preclinical insights into inflammatory responses in necrotizing enterocolitis.Seminars in immunopathology · 2025Review
- Article
- Necrotizing Enterocolitis: A Comprehensive Review on Toll-like Receptor 4-Mediated Pathophysiology, Clinical, and Therapeutic Insights.Biomedicines · 2025Review
- Bone marrow-derived mesenchymal stromal cells in necrotizing enterocolitis treatment: a narrative review.Frontiers in pediatrics · 2025Review
- Use of CatBoost algorithm to identify the need for surgery in infants with necrotizing enterocolitis.Frontiers in pediatrics · 2025Article
- Neutrophils aggravate inflammatory lesions in intestinal organoids from necrotizing enterocolitis.Frontiers in immunology · 2025Article
- Gut Microbiota and Liver Dysfunction in Sepsis: The Role of Inflammatory Mediators and Therapeutic Approaches.International journal of molecular sciences · 2024Review
- Network-Based Bioinformatics Highlights Broad Importance of Human Milk Hyaluronan.International journal of molecular sciences · 2024Article
- Evolutionary bridges: how factors present in amniotic fluid and human milk help mature the gut.Journal of perinatology : official journal of the California Perinatal Association · 2024Review
- Effect of Probiotics on Gastrointestinal Health Through the Aryl Hydrocarbon Receptor Pathway: A Systematic Review.Foods (Basel, Switzerland) · 2024Review
- Umbilical cord mesenchymal stem cell exosomes alleviate necrotizing enterocolitis in neonatal mice by regulating intestinal epithelial cells autophagy.World journal of stem cells · 2024Article
- Transcriptomic analysis of the effect of remote ischaemic conditioning in an animal model of necrotising enterocolitis.Scientific reports · 2024Article
- Neonatal Necrotizing Enterocolitis: An Update on Pathophysiology, Treatment, and Prevention.Paediatric drugs · 2024Review
40 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 2 institutions in 1 country.
Funding
Abstract
Necrotizing enterocolitis (NEC) develops in response to elevated TLR4 signaling in the newborn intestinal epithelium and is characterized by TLR4-mediated inhibition of enterocyte migration and reduced mucosal healing. The downstream processes by which TLR4 impairs mucosal healing remain incompletely understood. In other systems, TLR4 induces autophagy, an adaptive response to cellular stress. We now hypothesize that TLR4 induces autophagy in enterocytes and that TLR4-induced autophagy plays a critical role in NEC development. Using mice selectively lacking TLR4 in enterocytes (TLR4(ΔIEC)) and in TLR4-deficient cultured enterocytes, we now show that TLR4 activation induces autophagy in enterocytes. Immature mouse and human intestine showed increased expression of autophagy genes compared with full-term controls, and NEC development in both mouse and human was associated with increased enterocyte autophagy. Importantly, using mice in which we selectively deleted the autophagy gene ATG7 from the intestinal epithelium (ATG7(ΔIEC)), the induction of autophagy was determined to be required for and not merely a consequence of NEC, because ATG7(ΔIEC) mice were protected from NEC development. In defining the mechanisms involved, TLR4-induced autophagy led to impaired enterocyte migration both in vitro and in vivo, which in cultured enterocytes required the induction of RhoA-mediated stress fibers. These findings depart from current dogma in the field by identifying a unique effect of TLR4-induced autophagy within the intestinal epithelium in the pathogenesis of NEC and identify that the negative consequences of autophagy on enterocyte migration play an essential role in its development.
Indexed as
Identifiers
What OpenQuestion holds
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.