ArticleNature2012
Tissue factor and PAR1 promote microbiota-induced intestinal vascular remodelling.
Article in Nature, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 159 papers, 1 of them a synthesis that pooled it.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
159 citing papers in PubMed, 1 synthesis or guideline pooled it, 270 citations in OpenAlex.
- The role of the intestinal microbiome in antiphospholipid syndrome.Frontiers in immunology · 2022Pooled it
- Trial
- The intestinal microbiome potentially affects thrombin generation in human subjects.Journal of thrombosis and haemostasis : JTH · 2020Trial
- Gene Expression Analysis of Human Papillomavirus-Associated Colorectal Carcinoma.BioMed research international · 2020Trial
- The putative role of the microbiota in the development of neuropsychiatric disorders following early childhood malnutrition.Gut microbes · 2026Review
- Vitexin Alleviates Knee Osteoarthritis-Associated Cartilage Damage Associated with F3 Modulation.Genes · 2026Article
- Toll-like receptor 2 impacts small intestinal villus capillarization through epithelial dual oxidase 2.Redox biology · 2026Article
- Large temperature excursions have modest impacts on community composition in the high diversity gut microbiome of omnivorous American cockroaches (Microbiology spectrum · 2026Article
- Angiogenesis in Inflammatory Bowel Disease.Pharmaceuticals (Basel, Switzerland) · 2026Review
- State-of-the-Art Review on Probiotics, Synbiotics, and Microbial Metabolites: Molecular Mechanisms Shaping Host Immunity, Metabolic Health, and Chronic Disease Prevention.Molecular nutrition & food research · 2026Review
- Large temperature excursions have modest impacts on community composition in the high diversity gut microbiome of omnivorous American cockroaches (bioRxiv : the preprint server for biology · 2026Article
- From cooperation to collapse: the diet-microbiota-host gene triad in disease and aging.Frontiers in microbiomes · 2026Review
- Mechanisms of multi-organ damage in Wilson disease from the gut-liver-brain axis perspective: copper metabolism, gut microbiota, and metabolite communication.Frontiers in microbiology · 2026Review
- Computational prediction and conformation of relationships among microbes, drugs and diseases.Scientific reports · 2025Article
- Harnessing gut microbiota for colorectal cancer therapy: from clinical insights to therapeutic innovations.NPJ biofilms and microbiomes · 2025Review
- Synbiotics in Alzheimer's disease: mechanisms, clinical evidence, and therapeutic prospects.Journal of translational medicine · 2025Review
- Effects of the gut microbiota on placental angiogenesis and intrauterine growth in gnotobiotic mice.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Review
- Bioinformatics and experimental insights into F2RL1 as a key biomarker in cervical cancer diagnosis and prognosis.Scientific reports · 2025Article
- The gut microbiota in thrombosis.Nature reviews. Cardiology · 2025Review
99 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 4 institutions in 4 countries.
Funding
Abstract
The gut microbiota is a complex ecosystem that has coevolved with host physiology. Colonization of germ-free (GF) mice with a microbiota promotes increased vessel density in the small intestine, but little is known about the mechanisms involved. Tissue factor (TF) is the membrane receptor that initiates the extrinsic coagulation pathway, and it promotes developmental and tumour angiogenesis. Here we show that the gut microbiota promotes TF glycosylation associated with localization of TF on the cell surface, the activation of coagulation proteases, and phosphorylation of the TF cytoplasmic domain in the small intestine. Anti-TF treatment of colonized GF mice decreased microbiota-induced vascular remodelling and expression of the proangiogenic factor angiopoietin-1 (Ang-1) in the small intestine. Mice with a genetic deletion of the TF cytoplasmic domain or with hypomorphic TF (F3) alleles had a decreased intestinal vessel density. Coagulation proteases downstream of TF activate protease-activated receptor (PAR) signalling implicated in angiogenesis. Vessel density and phosphorylation of the cytoplasmic domain of TF were decreased in small intestine from PAR1-deficient (F2r(-/-)) but not PAR2-deficient (F2rl1(-/-)) mice, and inhibition of thrombin showed that thrombin-PAR1 signalling was upstream of TF phosphorylation. Thus, the microbiota-induced extravascular TF-PAR1 signalling loop is a novel pathway that may be modulated to influence vascular remodelling in the small intestine.
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What 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.