ArticleThe American journal of pathology2014
The neurotensin-HIF-1α-VEGFα axis orchestrates hypoxia, colonic inflammation, and intestinal angiogenesis.
Article in The American journal of pathology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 33 citations in OpenAlex.
- Toll-like receptor 2 impacts small intestinal villus capillarization through epithelial dual oxidase 2.Redox biology · 2026Article
- Angiogenesis in Inflammatory Bowel Disease.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Neurotensin drives theca cell migration during ovulation in primates†.Biology of reproduction · 2026Article
- Hypoxia-Induced Gut-Brain Axis Remodeling and Insomnia: Mechanisms and Microbiota Adaptive Regulation from a Translational Perspective.Journal of inflammation research · 2026Review
- Across Barriers: Blood-Brain and Gut Barrier Signaling in Psychiatric Disorders.Journal of neurochemistry · 2025Review
- Neurotensin Regulates Primate Ovulation Via Multiple Neurotensin Receptors.Endocrinology · 2025Article
- Hypoxia, hypoxia-inducible factors and inflammatory bowel diseases.Gastroenterology report · 2024Review
- Effects of extensive mobilization and tension anastomosis in anorectal reconstruction (experimental study).Pediatric surgery international · 2022Article
- Photobiomodulation reduces inflammation but does not influence the hypoxia-inducible factor-1α in pulp tissue of rats after bleaching.Journal of applied oral science : revista FOB · 2022Article
- In Silico and In Vivo Studies on the Mechanisms of Chinese Medicine Formula (Gegen Qinlian Decoction) in the Treatment of Ulcerative Colitis.Frontiers in pharmacology · 2021Article
- Homeoprotein OTX1 and OTX2 involvement in rat myenteric neuron adaptation after DNBS-induced colitis.PeerJ · 2020Article
- Clostridium difficile toxins induce VEGF-A and vascular permeability to promote disease pathogenesis.Nature microbiology · 2019Article
- Article
- Obesity and gastrointestinal cancer: the interrelationship of adipose and tumour microenvironments.Nature reviews. Gastroenterology & hepatology · 2018Review
- Review
- Endothelial Atg7 Deficiency Ameliorates Acute Cerebral Injury Induced by Ischemia/Reperfusion.Frontiers in neurology · 2018Article
- Role of G protein-coupled receptors-microRNA interactions in gastrointestinal pathophysiology.American journal of physiology. Gastrointestinal and liver physiology · 2017Review
- Analysis on regulatory network linked to Hpa gene in invasion and metastasis of colon cancer.Saudi journal of biological sciences · 2017Article
- Transcriptome Analysis Reveals Distinct Gene Expression Profiles in Eosinophilic and Noneosinophilic Chronic Rhinosinusitis with Nasal Polyps.Scientific reports · 2016Article
- Neurotensin Promotes the Development of Colitis and Intestinal Angiogenesis via Hif-1α-miR-210 Signaling.Journal of immunology (Baltimore, Md. : 1950) · 2016Article
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
The expression of neurotensin (NT) and its receptor (NTR1) is up-regulated in experimental colitis and inflammatory bowel disease; NT/NTR1 interactions regulate gut inflammation. During active inflammation, metabolic shifts toward hypoxia lead to the activation of hypoxia-inducible factor (HIF)-1, which enhances vascular endothelial growth factor (VEGF) expression, promoting angiogenesis. We hypothesized that NT/NTR1 signaling regulates intestinal manifestations of hypoxia and angiogenesis by promoting HIF-1 transcriptional activity and VEGFα expression in experimental colitis. We studied NTR1 signaling in colitis-associated angiogenesis using 2,4,6-trinitrobenzenesulfonic acid-treated wild-type and NTR1-knockout mice. The effects of NT on HIF-1α and VEGFα were assessed on human colonic epithelial cells overexpressing NTR1 (NCM460-NTR1) and human intestinal microvascular-endothelial cells. NTR1-knockout mice had reduced microvascular density and mucosal integrity score compared with wild-type mice after 2,4,6-trinitrobenzenesulfonic acid treatment. VEGFα mRNA levels were increased in NCM460-NTR1 cells treated with 10(-7) mol/L NT, at 1 and 6 hours post-treatment. NT exposure in NCM460-NTR1 cells caused stabilization, nuclear translocation, and transcriptional activity of HIF-1α in a diacylglycerol kinase-dependent manner. NT did not stimulate tube formation in isolated human intestinal macrovascular endothelial cells but did so in human intestinal macrovascular endothelial cells cocultured with NCM460-NTR1 cells. Our results demonstrate the importance of an NTR1-HIF-1α-VEGFα axis in intestinal angiogenic responses and in the pathophysiology of colitis and inflammatory bowel disease.
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