ArticleScience translational medicine2014
PHD inhibition mitigates and protects against radiation-induced gastrointestinal toxicity via HIF2.
Article in Science translational medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers, 1 of them a synthesis that pooled it.
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Who cites it
80 citing papers in PubMed, 1 synthesis or guideline pooled it, 131 citations in OpenAlex.
- The Therapeutic Relevance of Urolithins, Intestinal Metabolites of Ellagitannin-Rich Food: A Systematic Review of In Vivo Studies.Nutrients · 2022Pooled it
- Yin and Yang of ginsenosides: Molecular mechanisms of bidirectional regulation of angiogenesis.Journal of ginseng research · 2026Review
- 1,2-propanediol ameliorated radiation-induced intestinal injury in mice.Scientific reports · 2026Article
- Low-dose 5-hydroxymethylfurfural mitigates radiation -induced intestinal toxicity via HIF2α-driven IL22/STAT3 signaling enhancement.Journal of translational medicine · 2026Article
- Hypoxia-inducible factor-1α exacerbates immune injury induced by influenza A virus and Streptococcus pneumoniae coinfection.BMC infectious diseases · 2025Article
- Radiation-induced intestinal injury: from molecular mechanisms to clinical translation.Oncology reviews · 2025Review
- Prolyl hydroxylase domain inhibitor is an effective pre-hospital pharmaceutical intervention for trauma and hemorrhagic shock.Scientific reports · 2024Article
- Astragalus polysaccharide promotes the regeneration of intestinal stem cells through HIF-1 signalling pathway.Journal of cellular and molecular medicine · 2024Article
- Disruption of hypoxia-inducible factor-2α in neutrophils decreases colitis-associated colon cancer.American journal of physiology. Gastrointestinal and liver physiology · 2024Article
- Improving radiotherapy in immunosuppressive microenvironments by targeting complement receptor C5aR1.The Journal of clinical investigation · 2023Article
- Loss of prolyl hydroxylase 1 and 2 in SM22α-expressing cells prevents Hypoxia-Induced pulmonary hypertension.American journal of physiology. Lung cellular and molecular physiology · 2023Article
- Hypoxia and Intestinal Inflammation: Common Molecular Mechanisms and Signaling Pathways.International journal of molecular sciences · 2023Review
- Hypoxia inducible factor prolyl hydroxylases in inflammatory bowel disease.Frontiers in pharmacology · 2023Review
- Feasibility and guidelines for the use of an injectable fiducial marker (BioXmarkF1000Research · 2023Article
- SM22α cell-specific HIF stabilization mitigates hyperoxia-induced neonatal lung injury.American journal of physiology. Lung cellular and molecular physiology · 2022Article
- Inhibition of hypoxia-inducible factor-prolyl hydroxylation protects from cyclophosphamide-induced bladder injury and urinary dysfunction.American journal of physiology. Renal physiology · 2022Article
- FG-4592 protects the intestine from irradiation-induced injury by targeting the TLR4 signaling pathway.Stem cell research & therapy · 2022Article
- Stromal HIF2 Regulates Immune Suppression in the Pancreatic Cancer Microenvironment.Gastroenterology · 2022Article
- Study on the protective effect and mechanism of Liriodendrin on radiation enteritis in mice.Journal of radiation research · 2022Article
- Gut metabolite Urolithin A mitigates ionizing radiation-induced intestinal damage.Journal of cellular and molecular medicine · 2021Article
20 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Radiation-induced gastrointestinal (GI) toxicity can be a major source of morbidity and mortality after radiation exposure. There is an unmet need for effective preventative or mitigative treatments against the potentially fatal diarrhea and water loss induced by radiation damage to the GI tract. We report that prolyl hydroxylase inhibition by genetic knockout or pharmacologic inhibition of all PHD (prolyl hydroxylase domain) isoforms by the small-molecule dimethyloxallyl glycine (DMOG) increases hypoxia-inducible factor (HIF) expression, improves epithelial integrity, reduces apoptosis, and increases intestinal angiogenesis, all of which are essential for radioprotection. HIF2, but not HIF1, is both necessary and sufficient to prevent radiation-induced GI toxicity and death. Increased vascular endothelial growth factor (VEGF) expression contributes to the protective effects of HIF2, because inhibition of VEGF function reversed the radioprotection and radiomitigation afforded by DMOG. Additionally, mortality from abdominal or total body irradiation was reduced even when DMOG was given 24 hours after exposure. Thus, prolyl hydroxylase inhibition represents a treatment strategy to protect against and mitigate GI toxicity from both therapeutic radiation and potentially lethal radiation exposures.
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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.