ArticleJournal of Crohn's & colitis2016
M1 Macrophages Activate Notch Signalling in Epithelial Cells: Relevance in Crohn's Disease.
Article in Journal of Crohn's & colitis, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 65 citations in OpenAlex.
- The role of HIF-1α in innate immune mechanisms and autoimmunity: A double-edged sword.The Journal of biological chemistry · 2026Review
- GAS5 mediates notch signaling to exacerbate calcium oxalate-induced renal injury through the NF-κB/NLRP3 axis by promoting macrophage polarization.Cellular and molecular life sciences : CMLS · 2026Article
- Myeloid Mcpip1/Regnase-1 regulates intestinal homeostasis by modulating epithelial cell differentiation.BMC gastroenterology · 2026Article
- Activated notch signaling pathway protects the intestinal barrier in DSS-induced colitis by regulating tight junctions.European journal of medical research · 2026Article
- Identification of Crohn's disease-associated molecular signatures by integrative bioinformatics analysis and experimental validation.Frontiers in immunology · 2026Article
- Expression Profiles, Biological Functions and Clinical Significance of Circular RNAs in Inflammatory Bowel Disease.Journal of inflammation research · 2026Review
- Review
- The Role of Notch Signaling and Gut Microbiota in Autoinflammatory Diseases: Mechanisms and Future Views.Biomedicines · 2025Review
- Down-regulation of MIR-378A-3P expression associated with inflammation: The effects of restoring its levels.PloS one · 2025Article
- Inhibition of DLL4/Notch Signaling Pathway Promotes M2 Polarization and Cell Proliferation in Pulmonary Arterial Hypertension.ACS omega · 2024Article
- A Narrative Review: Immunometabolic Interactions of Host-Gut Microbiota and Botanical Active Ingredients in Gastrointestinal Cancers.International journal of molecular sciences · 2024Review
- M1 and M2 Macrophages Differentially Regulate Colonic Crypt Renewal.Inflammatory bowel diseases · 2024Article
- Delta- like ligand 4- expressing macrophages and human diseases: Insights into pathophysiology and therapeutic opportunities.Heliyon · 2023Review
- Emerging role of hypoxia-inducible factor-1α in inflammatory autoimmune diseases: A comprehensive review.Frontiers in immunology · 2022Review
- Is the Macrophage Phenotype Determinant for Fibrosis Development?Biomedicines · 2021Review
- Notch Signaling Pathway Is Activated by Sulfate Reducing Bacteria.Frontiers in cellular and infection microbiology · 2021Article
- Notch Signaling Ligand Jagged1 Enhances Macrophage-Mediated Response toFrontiers in microbiology · 2021Article
- A mutation in NOTCH2 gene first associated with Hajdu-Cheney syndrome in a Greek family: diversity in phenotype and response to treatment.Endocrine · 2021Article
- Pathogenic effects of inhibition of mTORC1/STAT3 axis facilitates Staphylococcus aureus-induced pyroptosis in human macrophages.Cell communication and signaling : CCS · 2020Article
- Review
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe Notch signalling pathway plays an essential role in mucosal regeneration, which constitutes a key goal of Crohn's disease (CD) treatment. Macrophages coordinate tissue repair and several phenotypes have been reported which differ in the expression of surface proteins, cytokines and hypoxia-inducible factors (HIFs). We analysed the role of HIFs in the expression of Notch ligands in macrophages and the relevance of this pathway in mucosal regeneration.
methodsHuman monocytes and U937-derived macrophages were polarized towards the M1 and M2 phenotypes and the expression levels of HIF-1α, HIF-2α, Jagged 1 (Jag1) and delta-like 4 (Dll4) were evaluated. The effects of macrophages on the expression of hairy and enhancer of split-1 (HES1, the main target of Notch signalling) and intestinal alkaline phosphatase (IAP, enterocyte marker) in epithelial cells in co-culture were also analysed. Phenotype macrophage markers and Notch signalling were evaluated in the mucosa of CD patients.
resultsM1 macrophages were associated with HIF-1-dependent induction of Jag1 and Dll4, which increased HES1 protein levels and IAP activity in co-cultured epithelial cells. In the mucosa of CD patients a high percentage of M1 macrophages expressed both HIF-1α and Jag1 while M2 macrophages mainly expressed HIF-2α and we detected a good correlation between the ratio of M1/M2 macrophages and both HES1 and IAP protein levels.
conclusionM1, but not M2, macrophages are associated with HIF-1-dependent induction of Notch ligands and activation of epithelial Notch signalling pathway. In the mucosa of chronic CD patients, the prevalence of M2 macrophages is associated with diminution of Notch signalling and impaired enterocyte differentiation.
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