ArticleThe American journal of pathology2014
The ErbB4 ligand neuregulin-4 protects against experimental necrotizing enterocolitis.
Article in The American journal of pathology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 69 citations in OpenAlex.
- Neuregulin 4 in Insulin Resistance: Mechanisms, Controversies, and Therapeutic Perspectives.Diabetes, metabolic syndrome and obesity : targets and therapy · 2026Review
- Adipocytokine profiles in maternal obesity: The impact of lipoinflammation on serum, breastmilk, and infant metabolic development.Clinical pediatric endocrinology : case reports and clinical investigations : official journal of the Japanese Society for Pediatric Endocrinology · 2025Review
- Protective effect of soluble protein hydrolysate against HMolecular medicine reports · 2025Article
- Adipokines as Cardioprotective Factors: BAT Steps Up to the Plate.Biomedicines · 2025Review
- Sodium formate induces development-dependent intestinal epithelial injury via necroptosis and apoptosis.Redox report : communications in free radical research · 2024Article
- Host defense peptides human β defensin 2 and LL-37 ameliorate murine necrotizing enterocolitis.iScience · 2024Article
- The journey towards physiology and pathology: Tracing the path of neuregulin 4.Genes & diseases · 2024Review
- Deletion of Endogenous Neuregulin-4 Limits Adaptive Immunity During Interleukin-10 Receptor-Neutralizing Colitis.Inflammatory bowel diseases · 2023Article
- SpatialDM for rapid identification of spatially co-expressed ligand-receptor and revealing cell-cell communication patterns.Nature communications · 2023Article
- Butyrate induces development-dependent necrotizing enterocolitis-like intestinal epithelial injury via necroptosis.Pediatric research · 2023Article
- State-of-the-art review and update ofFrontiers in pediatrics · 2023Review
- Nutritional deficiency in an intestine-on-a-chip recapitulates injury hallmarks associated with environmental enteric dysfunction.Nature biomedical engineering · 2022Article
- Article
- Neuregulin 4 as a novel adipokine in energy metabolism.Frontiers in physiology · 2022Review
- Metabolic model of necrotizing enterocolitis in the premature newborn gut resulting from enteric dysbiosis.Frontiers in pediatrics · 2022Article
- Neuregulin 4 Downregulation Induces Insulin Resistance in 3T3-L1 Adipocytes through Inflammation and Autophagic Degradation of GLUT4 Vesicles.International journal of molecular sciences · 2021Article
- Neuregulins in Neurodegenerative Diseases.Frontiers in aging neuroscience · 2021Article
- Early Postnatal Comprehensive Biomarkers Cannot Identify Extremely Preterm Infants at Risk of Developing Necrotizing Enterocolitis.Frontiers in pediatrics · 2021Article
- Article
- Neuregulin, an Effector on Mitochondria Metabolism That Preserves Insulin Sensitivity.Frontiers in physiology · 2020Review
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Necrotizing enterocolitis (NEC) affects up to 10% of premature infants, has a mortality of 30%, and can leave surviving patients with significant morbidity. Neuregulin-4 (NRG4) is an ErbB4-specific ligand that promotes epithelial cell survival. Thus, this pathway could be protective in diseases such as NEC, in which epithelial cell death is a major pathologic feature. We sought to determine whether NRG4-ErbB4 signaling is protective in experimental NEC. NRG4 was used i) in the newborn rat formula feeding/hypoxia model; ii) in a recently developed model in which 14- to 16-day-old mice are injected with dithizone to induce Paneth cell loss, followed by Klebsiella pneumoniae infection to induce intestinal injury; and iii) in bacterially infected IEC-6 cells in vitro. NRG4 reduced NEC incidence and severity in the formula feed/hypoxia rat model. It also reduced Paneth cell ablation-induced NEC and prevented dithizone-induced Paneth cell loss in mice. In vitro, cultured ErbB4(-/-) ileal epithelial enteroids had reduced Paneth cell markers and were highly sensitive to inflammatory cytokines. Furthermore, NRG4 blocked, through a Src-dependent pathway, Cronobacter muytjensii-induced IEC-6 cell apoptosis. The potential clinical relevance of these findings was demonstrated by the observation that NRG4 and its receptor ErbB4 are present in human breast milk and developing human intestine, respectively. Thus, NRG4-ErbB4 signaling may be a novel pathway for therapeutic intervention or prevention in NEC.
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