ArticleThe Journal of clinical investigation2010
Epimorphin deletion protects mice from inflammation-induced colon carcinogenesis and alters stem cell niche myofibroblast secretion.
Article in The Journal of clinical investigation, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 49 citations in OpenAlex.
- Activation and Functions of Col6a1+ Fibroblasts in Colitis-Associated Cancer.International journal of molecular sciences · 2023Article
- From birth to death: The hardworking life of Paneth cell in the small intestine.Frontiers in immunology · 2023Review
- Plasma membrane flipping of Syntaxin-2 regulates its inhibitory action on insulin granule exocytosis.Nature communications · 2022Article
- Stem cell and niche regulation in human short bowel syndrome.JCI insight · 2020Article
- Large intestine embryogenesis: Molecular pathways and related disorders (Review).International journal of molecular medicine · 2020Review
- Cellular Interactions in the Intestinal Stem Cell Niche.Archivum immunologiae et therapiae experimentalis · 2019Review
- Epimorphin regulates the intestinal stem cell niche via effects on the stromal microenvironment.American journal of physiology. Gastrointestinal and liver physiology · 2018Article
- Colon organoid formation and cryptogenesis are stimulated by growth factors secreted from myofibroblasts.PloS one · 2018Article
- Article
- The Effect of Sex on the Azoxymethane/Dextran Sulfate Sodium-treated Mice Model of Colon Cancer.Journal of cancer prevention · 2016Article
- CD90(+) stromal cells are the major source of IL-6, which supports cancer stem-like cells and inflammation in colorectal cancer.International journal of cancer · 2016Article
- Mechanisms of intestinal adaptation.Best practice & research. Clinical gastroenterology · 2016Review
- Mesenchymal-epithelial interactions during digestive tract development and epithelial stem cell regeneration.Cellular and molecular life sciences : CMLS · 2015Review
- Human esophageal myofibroblasts secrete proinflammatory cytokines in response to acid and Toll-like receptor 4 ligands.American journal of physiology. Gastrointestinal and liver physiology · 2015Article
- Effects of inflammation on stem cells: together they strive?EMBO reports · 2015Review
- Isolation of myofibroblasts from mouse and human esophagus.Journal of visualized experiments : JoVE · 2015Article
- Epimorphin expression in a rat model of pulmonary hypoplasia associated with congenital diaphragmatic hernia.Pediatric surgery international · 2014Article
- Tis7 deletion reduces survival and induces intestinal anastomotic inflammation and obstruction in high-fat diet-fed mice with short bowel syndrome.American journal of physiology. Gastrointestinal and liver physiology · 2014Article
- Epimorphin(-/-) mice are protected, in part, from acute colitis via decreased interleukin 6 signaling.Translational research : the journal of laboratory and clinical medicine · 2014Article
- NF-κB and Nrf2 signaling pathways contribute to wogonin-mediated inhibition of inflammation-associated colorectal carcinogenesis.Cell death & disease · 2014Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Epithelial-mesenchymal interactions regulate normal gut epithelial homeostasis and have a putative role in inflammatory bowel disease and colon cancer pathogenesis. Epimorphin is a mesenchymal and myofibroblast protein with antiproliferative, promorphogenic effects in intestinal epithelium. We previously showed that deletion of epimorphin partially protects mice from acute colitis, associated with an increase in crypt cell proliferation. Here we explored the potential therapeutic utility of modulating epimorphin expression by examining the effects of epimorphin deletion on chronic inflammation-associated colon carcinogenesis using the azoxymethane/dextran sodium sulfate (AOM/DSS) model. We found that mice in which epimorphin expression was absent had a marked reduction in incidence and extent of colonic dysplasia. Furthermore, epimorphin deletion in myofibroblasts altered the morphology and growth of cocultured epithelial cells. Loss of epimorphin affected secretion of soluble mesenchymal regulators of the stem cell niche such as Chordin. Importantly, IL-6 secretion from LPS-treated epimorphin-deficient myofibroblasts was completely inhibited, and stromal IL-6 expression was reduced in vivo. Taken together, these data show that epimorphin deletion inhibits chronic inflammation-associated colon carcinogenesis in mice, likely as a result of increased epithelial repair, decreased myofibroblast IL-6 secretion, and diminished IL-6-induced inflammation. Furthermore, we believe that modulation of epimorphin expression may have therapeutic benefits in appropriate clinical settings.
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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.