ArticleThe Journal of biological chemistry2012
Neuregulin-4 is a survival factor for colon epithelial cells both in culture and in vivo.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 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
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 52 citations in OpenAlex.
- The impact of serum neuregulin 4 (NRG-4) levels on non-alcoholic fatty liver disease (NAFLD): a systematic review and meta-analysis.BMC gastroenterology · 2025Pooled it
- Neuregulin 4 in Insulin Resistance: Mechanisms, Controversies, and Therapeutic Perspectives.Diabetes, metabolic syndrome and obesity : targets and therapy · 2026Review
- Neuregulin 4 inhibits synovial macrophage pro-inflammatory polarization via ErbB4/Stat5b/NF-κB signaling to alleviate osteoarthritis progression.Journal of orthopaedic surgery and research · 2025Article
- Dynamic alterations and clinical implications of the plasma proteome in pediatric sepsis.European journal of medical research · 2025Article
- The journey towards physiology and pathology: Tracing the path of neuregulin 4.Genes & diseases · 2024Review
- Neuregulin-1 and ALS19 (ERBB4): at the crossroads of amyotrophic lateral sclerosis and cancer.BMC medicine · 2024Review
- Deletion of Endogenous Neuregulin-4 Limits Adaptive Immunity During Interleukin-10 Receptor-Neutralizing Colitis.Inflammatory bowel diseases · 2023Article
- Implications of the Serum Concentrations of Neuregulin-4 (Nrg4) in Patients with Coronary Artery Disease: A Case-Control Study.The journal of Tehran Heart Center · 2023Article
- Nutritional deficiency in an intestine-on-a-chip recapitulates injury hallmarks associated with environmental enteric dysfunction.Nature biomedical engineering · 2022Article
- Role of ErbB1 in the Underlying Mechanism of Lapatinib-Induced Diarrhoea: A Review.BioMed research international · 2022Review
- Neuregulin 4 as a novel adipokine in energy metabolism.Frontiers in physiology · 2022Review
- Neuregulin 4 Downregulation Induces Insulin Resistance in 3T3-L1 Adipocytes through Inflammation and Autophagic Degradation of GLUT4 Vesicles.International journal of molecular sciences · 2021Article
- NRG4-ErbB4 signaling represses proinflammatory macrophage activity.American journal of physiology. Gastrointestinal and liver physiology · 2021Article
- Emerging Roles for Browning of White Adipose Tissue in Prostate Cancer Malignant Behaviour.International journal of molecular sciences · 2021Review
- Sprouty2 limits intestinal tuft and goblet cell numbers through GSK3β-mediated restriction of epithelial IL-33.Nature communications · 2021Article
- Neuregulins in Neurodegenerative Diseases.Frontiers in aging neuroscience · 2021Article
- IL-33-ST2 axis regulates myeloid cell differentiation and activation enabling effective club cell regeneration.Nature communications · 2020Article
- Neuregulin, an Effector on Mitochondria Metabolism That Preserves Insulin Sensitivity.Frontiers in physiology · 2020Review
- Transplantation of neuregulin 4-overexpressing adipose-derived mesenchymal stem cells ameliorates insulin resistance by attenuating hepatic steatosis.Experimental biology and medicine (Maywood, N.J.) · 2019Article
- Neuregulin in Health and Disease.International journal of brain disorders and treatment · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Expression of the ErbB4 tyrosine kinase is elevated in colonic epithelial cells during inflammatory bowel disease, whereas ErbB4 overexpression in cultured colonocytes blocks TNF-induced apoptosis in a ligand-dependent manner. Together, these observations suggest that ErbB4 induction may be a protective response. However, the effects of ErbB4 signaling in the colonic epithelium in vivo are not known. Furthermore, previous work on ErbB4 used ligands shared with other receptors, raising the question of whether the observed responses are explicitly due to ErbB4. In this study, we used the ErbB4-specific ligand neuregulin-4 (NRG4) to activate ErbB4 and define its role in colonocyte biology. NRG4 treatment, either in cultured cells or in mice, blocked colonic epithelial apoptosis induced by TNF and IFN-γ. It was also protective in a murine experimental colitis model. NRG4 stimulated phosphorylation of ErbB4 but not other ErbB receptors, indicating that this is a specific response. Furthermore, in contrast to related ligands, NRG4 enhanced cell survival but not proliferation or migration, and stimulated phosphorylation of the anti-apoptotic mediator Akt but not ERK MAPK. Pharmacological inhibition of PI3K/Akt signaling reversed the anti-apoptotic effects of NRG4, confirming the role of this cascade in NRG4-induced cell survival. With regard to the potential clinical importance of this pathway, NRG4 expression was decreased in human inflammatory bowel disease samples and mouse models of colitis, suggesting that activation of ErbB4 is altered in disease. Thus, exogenous NRG4 may be beneficial for disorders in which epithelial apoptosis is part of the pathology.
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.