ArticlePloS one2011
MicroRNA-449a overexpression, reduced NOTCH1 signals and scarce goblet cells characterize the small intestine of celiac patients.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 52 papers, 3 of them syntheses that pooled it.
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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.
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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.
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Who cites it
52 citing papers in PubMed, 3 syntheses or guidelines pooled it, 99 citations in OpenAlex.
- Clinical Significance of Mucin Signatures in Inflammatory Bowel Diseases: A Systematic Review of Their Expression Patterns, Polymorphisms, and Post-translational Modifications.Inflammatory bowel diseases · 2026Pooled it
- Pooled it
- Circulating miRNAs as Potential Biomarkers for Celiac Disease Development.Frontiers in immunology · 2021Pooled it
- Genome-Wide Transcriptomic Analysis of Intestinal Mucosa in Celiac Disease Patients on a Gluten-Free Diet and Postgluten Challenge.Cellular and molecular gastroenterology and hepatology · 2021Trial
- Epigenetic regulation by gut microbiota-derived metabolites in celiac disease.Biochemistry and biophysics reports · 2026Review
- Intestinal stem cell niche: An upcoming area of immense importance in gastrointestinal disorders.Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology · 2025Review
- miR-449a: A Promising Biomarker and Therapeutic Target in Cancer and Other Diseases.Cell biochemistry and biophysics · 2024Review
- MiR-1290: a potential therapeutic target for regenerative medicine or diagnosis and treatment of non-malignant diseases.Clinical and experimental medicine · 2023Review
- Changes of Enterocyte Morphology and Enterocyte: Goblet Cell Ratios in Dogs with Protein-Losing and Non-Protein-Losing Chronic Enteropathies.Veterinary sciences · 2023Article
- The protective role ofFrontiers in medicine · 2023Article
- Circulating Extracellular Vesicles Are Increased in Newly Diagnosed Celiac Disease Patients.Nutrients · 2022Article
- Celiac Disease and Neurological Manifestations: From Gluten to Neuroinflammation.International journal of molecular sciences · 2022Review
- Celiac disease: From genetics to epigenetics.World journal of gastroenterology · 2022Review
- Expression of Selected Genes and Circulating microRNAs in Patients with Celiac Disease.Medicina (Kaunas, Lithuania) · 2022Article
- Extracellular vesicle microRNAs in celiac disease patients under a gluten-free diet, and in lactose intolerant individuals.BBA advances · 2022Article
- A Combined mRNA- and miRNA-Sequencing Approach Reveals miRNAs as Potential Regulators of the Small Intestinal Transcriptome in Celiac Disease.International journal of molecular sciences · 2021Article
- Molecular Biomarkers for Celiac Disease: Past, Present and Future.International journal of molecular sciences · 2020Review
- Understanding human gut diseases at single-cell resolution.Human molecular genetics · 2020Review
- Fecal microRNAs as Innovative Biomarkers of Intestinal Diseases and Effective Players in Host-Microbiome Interactions.Cancers · 2020Review
- Dietary Gluten and Neurodegeneration: A Case for Preclinical Studies.International journal of molecular sciences · 2020Review
Corrections and comments
- Erratum issued
Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
MiRNAs play a relevant role in regulating gene expression in a variety of physiological and pathological conditions including autoimmune disorders. MiRNAs are also important in the differentiation and function of the mouse intestinal epithelium. Our study was aimed to look for miRNA-based modulation of gene expression in celiac small intestine, and particularly for genes involved in cell intestinal differentiation/proliferation mechanisms. A cohort of 40 children (20 with active CD, 9 on a gluten-free diet (GFD), and 11 controls), were recruited at the Paediatrics Department (University of Naples Federico II). The expression of 365 human miRNAs was quantified by TaqMan low-density arrays. We used bioinformatics to predict putative target genes of miRNAs and to select biological pathways. The presence of NOTCH1, HES1, KLF4, MUC-2, Ki67 and beta-catenin proteins in the small intestine of CD and control children was tested by immunohistochemistry. The expression of about 20% of the miRNAs tested differed between CD and control children. We found that high miR-449a levels targeted and reduced both NOTCH1 and KLF4 in HEK-293 cells. NOTCH1, KLF4 signals and the number of goblet cells were lower in small intestine of children with active CD and in those on a GFD than in controls, whereas more nuclear beta-catenin staining, as a sign of the WNT pathway activation, and more Ki67 staining, as sign of proliferation, were present in crypts from CD patients than in controls. In conclusion we first demonstrate a miRNA mediated gene regulation in small intestine of CD patients. We also highlighted a reduced NOTCH1 pathway in our patients, irrespective of whether the disease was active or not. We suggest that NOTCH pathway could be constitutively altered in the celiac small intestine and could drive the increased proliferation and the decreased differentiation of intestinal cells towards the secretory goblet cell lineage.
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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.