ArticleCellular and molecular life sciences : CMLS2020
Thalidomide targets EGFL6 to inhibit EGFL6/PAX6 axis-driven angiogenesis in small bowel vascular malformation.
Article in Cellular and molecular life sciences : CMLS, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 20 citations in OpenAlex.
- Targeting CRBN With Thalidomide Suppresses Fibrosis After Glaucoma Drainage Surgery Through NF-κB Pathway Inhibition.Investigative ophthalmology & visual science · 2026Article
- 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
- Rifaximin Inhibits Small Bowel Angiodysplasia-Associated Angiogenesis by Attenuating LncRNA-HIF1A-AS2/miR-153-3p/HIF-1 α/Ang-2 Axis.Current medical science · 2025Article
- Single-cell RNA-seq data have prevalent blood contamination but can be rescued by Originator, a computational tool separating single-cell RNA-seq by genetic and contextual information.Genome biology · 2025Article
- Single-cell RNA-Seq data have prevalent blood contamination but can be rescued by Originator, a computational tool separating single-cell RNA-Seq by genetic and contextual information.bioRxiv : the preprint server for biology · 2025Article
- Hypoxia and low-glucose environments co-induced HGDILnc1 promote glycolysis and angiogenesis.Cell death discovery · 2024Article
- Single-Cell Transcriptomics Reveals Cellular Heterogeneity and Complex Cell-Cell Communication Networks in the Mouse Cornea.Investigative ophthalmology & visual science · 2023Article
- Thalidomide upper limb embryopathy - pathogenesis, past and present management and future considerations.The Journal of hand surgery, European volume · 2023Review
- Thalidomide interaction with inflammation in idiopathic pulmonary fibrosis.Inflammopharmacology · 2023Review
- Tranexamic acid may be a useful pharmacotherapy for endoscopically resistant small bowel angiodysplasia.World journal of gastroenterology · 2023Review
- Low expression of FOXP2 predicts poor survival and targets caspase-1 to inhibit cell pyroptosis in colorectal cancer.Journal of Cancer · 2022Article
- Progress of EGFL6 in angiogenesis and tumor development.International journal of clinical and experimental pathology · 2022Review
- EGFL6 regulates angiogenesis and osteogenesis in distraction osteogenesis via Wnt/β-catenin signaling.Stem cell research & therapy · 2021Article
- Dynamic Enhancement Pattern on CT for Predicting Pancreatic Neuroendocrine Neoplasms with Low PAX6 Expression: A Retrospective Observational Study.Diagnostics (Basel, Switzerland) · 2020Article
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundSmall bowel vascular malformation disease (SBVM) is the most common cause of obscure gastrointestinal bleeding (OGIB). Several studies suggested that EGFL6 was able to promote the growth of tumor endothelial cells by forming tumor vessels. To date, it remains unclear how EGFL6 promotes pathological angiogenesis in SBVM and whether EGFL6 is a target of thalidomide.
methodsWe took advantage of SBVM plasma and tissue samples and compared the expression of EGFL6 between SBVM patients and healthy people via ELISA and Immunohistochemistry. We elucidated the underlying function of EGFL6 in SBVM in vitro and by generating a zebrafish model that overexpresses EGFL6, The cycloheximide (CHX)-chase experiment and CoIP assays were conducted to demonstrate that thalidomide can promote the degradation of EGFL6 by targeting CRBN.
resultsThe analysis of SBVM plasma and tissue samples revealed that EGFL6 was overexpressed in the patients compared to healthy people. Using in vitro and in vivo assays, we demonstrated that an EMT pathway triggered by the EGFL6/PAX6 axis is involved in the pathogenesis of SBVM. Furthermore, through in vitro and in vivo assays, we elucidated that thalidomide can function as anti-angiogenesis medicine through the regulation of EGFL6 in a proteasome-dependent manner. Finally, we found that CRBN can mediate the effect of thalidomide on EGFL6 expression and that the CRBN protein interacts with EGFL6 via a Lon N-terminal peptide.
conclusionOur findings revealed a key role for EGFL6 in SBVM pathogenesis and provided a mechanism explaining why thalidomide can cure small bowel bleeding resulting from SBVM.
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