ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2016
mTOR disruption causes intestinal epithelial cell defects and intestinal atrophy postinjury in mice.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
What it found
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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
70 citing papers in PubMed, 110 citations in OpenAlex.
- AP-1B Controls Several Levels of Cell Proliferation and Differentiation in Mouse Enteroids.Biology of the cell · 2026Article
- Nuclear Factor Y controls nutrient-adaptive epithelial growth by regulating mTOR in the Drosophila midgut.Development (Cambridge, England) · 2026Article
- Unraveling the pleiotropic roles of the mTOR-glycolytic axis in ulcerative colitis: from immunometabolic dysregulation to mucosal barrier remodeling.Frontiers in immunology · 2026Review
- Tissue-adapted Tregs harness inflammatory signals to promote intestinal repair from therapy-related injury.Signal transduction and targeted therapy · 2025Article
- The microbial metabolite desaminotyrosine protects against graft-versus-host disease via mTORC1 and STING-dependent intestinal regeneration.Nature communications · 2025Article
- Enteroendocrine cell differentiation: Implications for human disease.Molecular and cellular endocrinology · 2025Review
- Comparative effects of dietary sodium butyrate and tributyrin on broiler chickens' performance, gene expression, intestinal histomorphometry, blood indices, and litter.Scientific reports · 2025Article
- Immunosuppressant imprecision: multidirectional effects on metabolism and microbiome.Clinical microbiology reviews · 2025Review
- Shared requirement for MYC upstream super-enhancer region in tissue regeneration and cancer.Life science alliance · 2025Article
- Therapeutic targeting of the NOTCH1 and neddylation pathways in T cell acute lymphoblastic leukemia.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- The Mechanistic Target of Rapamycin MediatesMicroorganisms · 2025Article
- EGF receptor in organ development, tissue homeostasis and regeneration.Journal of biomedical science · 2025Review
- Network-Based Bioinformatics Highlights Broad Importance of Human Milk Hyaluronan.International journal of molecular sciences · 2024Article
- Comparative Analysis of Commercial and Home-Made Media on RSPO1/S6R Axis in Organoids with Different Wnt Backgrounds: A Methodological Guide for the Selection of Intestinal Patient-Derived Organoids Culture Media.International journal of molecular sciences · 2024Article
- Activation of fetal-like molecular programs during regeneration in the intestine and beyond.Cell stem cell · 2024Review
- Cbl and Cbl-b ubiquitin ligases are essential for intestinal epithelial stem cell maintenance.iScience · 2024Article
- Effects of methionine supplementation in a reduced protein diet on growth performance, oxidative status, intestinal health, oocyst shedding, and methionine and folate metabolism in broilers under Eimeria challenge.Journal of animal science and biotechnology · 2024Article
- Mechanisms driving fasting-induced protection from genotoxic injury in the small intestine.American journal of physiology. Gastrointestinal and liver physiology · 2024Article
- SIRT4 loss reprograms intestinal nucleotide metabolism to support proliferation following perturbation of homeostasis.Cell reports · 2024Article
- Amino acid transporter SLC7A5 regulates cell proliferation and secretary cell differentiation and distribution in the mouse intestine.International journal of biological sciences · 2024Article
10 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Intestinal stem cells (ISCs) drive small intestinal epithelial homeostasis and regeneration. Mechanistic target of rapamycin (mTOR) regulates stem and progenitor cell metabolism and is frequently dysregulated in human disease, but its physiologic functions in the mammalian small intestinal epithelium remain poorly defined. We disrupted the genes mTOR, Rptor, Rictor, or both Rptor and Rictor in mouse ISCs, progenitors, and differentiated intestinal epithelial cells (IECs) using Villin-Cre. Mutant tissues and wild-type or heterozygous littermate controls were analyzed by histologic immunostaining, immunoblots, and proliferation assays. A total of 10 Gy irradiation was used to injure the intestinal epithelium and induce subsequent crypt regeneration. We report that mTOR supports absorptive enterocytes and secretory Paneth and goblet cell function while negatively regulating chromogranin A-positive enteroendocrine cell number. Through additional Rptor, Rictor, and Rptor/Rictor mutant mouse models, we identify mechanistic target of rapamycin complex 1 as the major IEC regulatory pathway, but mechanistic target of rapamycin complex 2 also contributes to ileal villus maintenance and goblet cell size. Homeostatic adult small intestinal crypt cell proliferation, survival, and canonical wingless-int (WNT) activity are not mTOR dependent, but Olfm4(+) ISC/progenitor population maintenance and crypt regeneration postinjury require mTOR. Overall, we conclude that mTOR regulates multiple IEC lineages and promotes stem and progenitor cell activity during intestinal epithelium repair postinjury.
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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.