ArticleScientific reports2016
HIF-1α and HIF-2α induced angiogenesis in gastrointestinal vascular malformation and reversed by thalidomide.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 2 of them syntheses that pooled it.
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Who cites it
27 citing papers in PubMed, 2 syntheses or guidelines pooled it, 42 citations in OpenAlex.
- Safety of HIF prolyl hydroxylase inhibitors for anemia in dialysis patients: a systematic review and network meta-analysis.Frontiers in pharmacology · 2023Pooled it
- Thalidomide combined with transcatheter artierial chemoembolzation for primary hepatocellular carcinoma: a systematic review and meta-analysis.Oncotarget · 2017Pooled it
- Beyond VEGF: AEG-1/MTDH as a Systems-Level Orchestrator of Angiogenesis in Hepatocellular Carcinoma.Cells · 2026Review
- Renaissance of Phoenix Drug Thalidomide-New Insights into Practical Clinical Application and Optimization Strategies for Managing Adverse Effects in Digestive Diseases.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Endothelial HIF2α suppresses retinal angiogenesis in neonatal mice by upregulating NOTCH signaling.Development (Cambridge, England) · 2024Article
- Hypoxia and low-glucose environments co-induced HGDILnc1 promote glycolysis and angiogenesis.Cell death discovery · 2024Article
- Article
- Review
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- A reappraisal of the pharmacologic management of gastrointestinal bleeding in patients with continuous flow left ventricular assist devices.Heart failure reviews · 2021Review
- Hypoxia and its possible relationship with endometrial receptivity in adenomyosis: a preliminary study.Reproductive biology and endocrinology : RB&E · 2021Article
- Recent Developments in Extracellular Matrix Remodeling for Fat Grafting.Frontiers in cell and developmental biology · 2021Review
- Thalidomide targets EGFL6 to inhibit EGFL6/PAX6 axis-driven angiogenesis in small bowel vascular malformation.Cellular and molecular life sciences : CMLS · 2020Article
- Thalidomide for refractory gastrointestinal bleeding from vascular malformations in patients with significant comorbidities.World journal of clinical cases · 2020Article
- EPAS1 and VEGFA gene variants are related to the symptoms of acute mountain sickness in Chinese Han population: a cross-sectional study.Military Medical Research · 2020Article
- Substance P participates in periodontitis by upregulating HIF-1α and RANKL/OPG ratio.BMC oral health · 2020Article
- Hypoxia‑inducible factors in hepatocellular carcinoma (Review).Oncology reports · 2020Review
- Deletion of narfl leads to increased oxidative stress mediated abnormal angiogenesis and digestive organ defects in zebrafish.Redox biology · 2020Article
- Intrabody against prolyl hydroxylase 2 promotes angiogenesis by stabilizing hypoxia-inducible factor-1α.Scientific reports · 2019Article
- Glucose-6-Phosphate Upregulates Txnip Expression by Interacting With MondoA.Frontiers in molecular biosciences · 2019Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Thalidomide is used in clinical practice to treat gastrointestinal vascular malformation (GIVM), but the pathogenesis of GIVM is not clear. Hypoxia inducible factor 1 alpha (HIF-1α) and 2 alpha (HIF-2α/EPAS1) are in the same family and act as master regulators of the adaptive response to hypoxia. HIF-1α and HIF-2α are up-regulated in vascular malformations in intestinal tissues from GIVM patients, but not in adjacent normal vessels. Therefore, we investigated the role of HIF-1α and HIF-2α during angiogenesis and the mechanism of thalidomide action. In vitro experiments confirmed that vascular endothelial growth factor (VEGF) was a direct target of HIF-2α and that HIF-1α and HIF-2α regulated NOTCH1, Ang2, and DLL4, which enhanced vessel-forming of endothelial cells. Thalidomide down-regulated the expression of HIF-1α and HIF-2α and inhibited angiogenesis. In vivo zebrafish experiments suggested that HIF-2α overexpression was associated with abnormal subintestinal vascular (SIV) sprouting, which was reversed by thalidomide. This result indicated that thalidomide regulated angiogenesis via the inhibition of HIF-1α and HIF-2α expression, which further regulated downstream factors, including VEGF, NOTCH1, DLL4, and Ang2. The abnormally high expression of HIF-1α and HIF-2α may contribute to GIVM.
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