ArticleAnnals of clinical and laboratory science2012
SMAD4 haploinsufficiency associates with augmented colonic inflammation in select humans and mice.
Article in Annals of clinical and laboratory science, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
What it found
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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.
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.
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Who cites it
14 citing papers in PubMed, 17 citations in OpenAlex.
- Early-life Wnt4 expressing colon stromal cells orchestrate lifelong mucosal homeostasis via BMP-driven iNKT cell imprinting.Nature communications · 2026Article
- Navigating Drug Discovery for Myhre Syndrome: The Complexity of a Multisystemic Rare Disease.American journal of medical genetics. Part C, Seminars in medical genetics · 2025Review
- Epithelial-specific loss of Smad4 alleviates the fibrotic response in an acute colitis mouse model.Life science alliance · 2024Article
- Bacterial driver-passenger model in biofilms: a new mechanism in the development of colorectal cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2022Review
- The Role of Intestinal Microbiota in Colorectal Cancer.Frontiers in pharmacology · 2021Review
- Molecular Targets in Precision Chemoprevention of Colorectal Cancer: An Update from Pre-Clinical to Clinical Trials.International journal of molecular sciences · 2020Review
- The role of microbiota in the development of colorectal cancer.International journal of cancer · 2019Review
- Infection with enteric pathogens Salmonella typhimurium and Citrobacter rodentium modulate TGF-beta/Smad signaling pathways in the intestine.Gut microbes · 2018Article
- Mendelian Disease Associations Reveal Novel Insights into Inflammatory Bowel Disease.Inflammatory bowel diseases · 2018Article
- SMAD4 Protein Expression Is Downregulated in Ileal Epithelial Cells from Patients with Crohn's Disease with Significant Inverse Correlation to Disease Activity.Gastroenterology research and practice · 2018Article
- TGF-β in inflammatory bowel disease: a key regulator of immune cells, epithelium, and the intestinal microbiota.Journal of gastroenterology · 2017Review
- Loss of n-6 fatty acid induced pediatric obesity protects against acute murine colitis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2015Article
- Identification of a novel heterozygous truncation mutation in exon 1 of ARHGAP29 in an Indian subject with nonsyndromic cleft lip with cleft palate.European journal of dentistry · 2014Article
- A strategy to identify dominant point mutant modifiers of a quantitative trait.G3 (Bethesda, Md.) · 2014Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
SMAD4 is a common mediator of the TGF-beta signaling pathway. One of the members of this pathway, TGF-beta 1, has an important role in controlling gut inflammation in relation to the continuous stimulation of the intestinal microbiota. SMAD4 haploinsufficiency in humans has been linked to juvenile polyposis hereditary hemorrhagic telangiectasia syndrome (JP/HHT; OMIM#17505). Hematochezia and colonic mucosal inflammation suggestive of inflammatory bowel diseases (IBD) have been reported in JP/HHT. Stimulated by recent experience with two affected pediatric patients presented here, we explored the potential role of Smad4 haploinsufficiency in a murine model of colonic inflammation. Smad4(+/-) mice were maintained on a mixed C57/129SvEv background. Chronic colitis was induced with repeated administration of dextran sulfate sodium (DSS) in drinking water. The colonic mucosal microbiota was interrogated by massively parallel pyrosequencing of the bacterial 16S rRNA gene. 66.7% of Smad4(+/-) mice were sensitive to DSS colitis compared to 14.3% of wild type (Chi-Square p=0.036). The augmented colitis was associated with microbiota separation in the Smad4(+/-) mice. Enterococcus and Enterococcus faecalis specifically was increased in abundance in the colitis-prone animals. Smad4 haploinsufficiency can associate with increased susceptibility to large bowel inflammation in mammals with variable penetrance in association with the colonic mucosal microbiota. These findings may reveal implications not only towards colonic inflammation in the setting of SMAD4 haploinsufficiency, but for colorectal cancer as well.
Indexed as
Identifiers
23090737PMC3875295W2133880193What 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.