ArticleThe Journal of clinical investigation2014
Heparan sulfate deficiency disrupts developmental angiogenesis and causes congenital diaphragmatic hernia.
Article in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 68 citations in OpenAlex.
- Sonic hedgehog reduces alveolar bone resorption by triggering the coupling of type H vessel formation and osteogenesis in a periodontitis model.BMC oral health · 2026Article
- Pulmonary T2* quantification of fetuses with congenital diaphragmatic hernia: a retrospective, case-controlled, MRI pilot study.Pediatric research · 2026Article
- Brain vascular stability relies on PAK2-cilia-PDGF-BB-HSPGs on basolateral side of endothelium.Life science alliance · 2026Article
- MMP2 sheds Glypican-4 to suppress Slit3-Robo4 signaling and angiogenesis.Proteoglycan research · 2026Article
- Emerging Role of the Slit/Roundabout (Robo) Signaling Pathway in Glioma Pathogenesis and Potential Therapeutic Options.Biomolecules · 2024Review
- Novel insights into the roles of migrasome in cancer.Discover oncology · 2024Review
- Identification of New Markers of Angiogenic Sprouting Using Transcriptomics: New Role for RND3.Arteriosclerosis, thrombosis, and vascular biology · 2024Article
- The Role of SLIT3-ROBO4 Signaling in Endoplasmic Reticulum Stress-Induced Delayed Corneal Epithelial and Nerve Regeneration.Investigative ophthalmology & visual science · 2024Article
- Vascular Heparan Sulfate and Amyloid-β in Alzheimer's Disease Patients.International journal of molecular sciences · 2024Article
- Heparan sulfate proteoglycan in Alzheimer's disease: aberrant expression and functions in molecular pathways related to amyloid-β metabolism.American journal of physiology. Cell physiology · 2023Review
- Role of the SLIT-ROBO signaling pathway in renal pathophysiology and various renal diseases.Frontiers in physiology · 2023Review
- Molecular dynamics-based descriptors of 3-O-Sulfated Heparan sulfate as contributors of protein binding specificity.Computational biology and chemistry · 2022Article
- Robo4 is constitutively shed by ADAMs from endothelial cells and the shed Robo4 functions to inhibit Slit3-induced angiogenesis.Scientific reports · 2022Article
- Physiology and Pathophysiology of Heparan Sulfate in Animal Models: Its Biosynthesis and Degradation.International journal of molecular sciences · 2022Review
- Genetically Modified Mouse Models of Congenital Diaphragmatic Hernia: Opportunities and Limitations for Studying Altered Lung Development.Frontiers in pediatrics · 2022Review
- Dissociation of DNA damage sensing by endoglycosidase HPSE.iScience · 2021Article
- STK35 Gene Therapy Attenuates Endothelial Dysfunction and Improves Cardiac Function in Diabetes.Frontiers in cardiovascular medicine · 2021Article
- Heparan Sulfate Facilitates Spike Protein-Mediated SARS-CoV-2 Host Cell Invasion and Contributes to Increased Infection of SARS-CoV-2 G614 Mutant and in Lung Cancer.Frontiers in molecular biosciences · 2021Article
- Transgenic animal models of congenital diaphragmatic hernia: a comprehensive overview of candidate genes and signaling pathways.Pediatric surgery international · 2020Review
- Heparan sulfate inhibits transforming growth factor β signaling and functions in cis and in trans to regulate prostate stem/progenitor cell activities.Glycobiology · 2020Article
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Authors and funding
18 authors at 4 institutions in 2 countries.
Funding
Abstract
Congenital diaphragmatic hernia (CDH) is a common birth malformation with a heterogeneous etiology. In this study, we report that ablation of the heparan sulfate biosynthetic enzyme NDST1 in murine endothelium (Ndst1ECKO mice) disrupted vascular development in the diaphragm, which led to hypoxia as well as subsequent diaphragm hypoplasia and CDH. Intriguingly, the phenotypes displayed in Ndst1ECKO mice resembled the developmental defects observed in slit homolog 3 (Slit3) knockout mice. Furthermore, introduction of a heterozygous mutation in roundabout homolog 4 (Robo4), the gene encoding the cognate receptor of SLIT3, aggravated the defect in vascular development in the diaphragm and CDH. NDST1 deficiency diminished SLIT3, but not ROBO4, binding to endothelial heparan sulfate and attenuated EC migration and in vivo neovascularization normally elicited by SLIT3-ROBO4 signaling. Together, these data suggest that heparan sulfate presentation of SLIT3 to ROBO4 facilitates initiation of this signaling cascade. Thus, our results demonstrate that loss of NDST1 causes defective diaphragm vascular development and CDH and that heparan sulfate facilitates angiogenic SLIT3-ROBO4 signaling during vascular development.
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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.