ArticleScientific reports2017
G-protein coupled receptor 15 mediates angiogenesis and cytoprotective function of thrombomodulin.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.
- The Biological and Clinical Relevance of G Protein-Coupled Receptors to the Outcomes of Hematopoietic Stem Cell Transplantation: A Systematized Review.International journal of molecular sciences · 2019Pooled it
- A timeless chronicle: Effects of cigarette smoke on GPR15 receptor and its oncogenic potential.Cancer letters · 2026Review
- Article
- Thrombomodulin: A key regulator of intravascular blood coagulation, fibrinolysis, and inflammation, and a treatment for disseminated intravascular coagulation.Proceedings of the Japan Academy. Series B, Physical and biological sciences · 2025Review
- A Novel Mitochondria-Associated Programmed Cell Death-Related Prognostic Model and Validation of Oncogene INHBB in Colorectal Cancer.International journal of genomics · 2025Article
- Tree of life: endothelial cell in norm and disease, the good guy is a partner in crime!Anatomy & cell biology · 2023Review
- From multi-omics approaches to personalized medicine in myocardial infarction.Frontiers in cardiovascular medicine · 2023Review
- Emerging roles of a chemoattractant receptor GPR15 and ligands in pathophysiology.Frontiers in immunology · 2023Review
- Endogenous Peptide Inhibitors of HIV Entry.Advances in experimental medicine and biology · 2022Article
- The Role of GPR15 Function in Blood and Vasculature.International journal of molecular sciences · 2021Review
- Article
- Advances in the diagnosis and treatment of disseminated intravascular coagulation in haematological malignancies.International journal of hematology · 2021Review
- C-type lectin domain group 14 proteins in vascular biology, cancer and inflammation.The FEBS journal · 2019Review
- Identification of time‑series differentially expressed genes and pathways associated with heart failure post‑myocardial infarction using integrated bioinformatics analysis.Molecular medicine reports · 2019Article
- Thrombomodulin Regulation of Mitogen-Activated Protein Kinases.International journal of molecular sciences · 2019Review
- Cytoprotective and pro-angiogenic functions of thrombomodulin are preserved in the C loop of the fifth epidermal growth factor-like domain.Haematologica · 2018Article
- Novel DNA Methylation Sites InfluenceBiomolecules · 2018Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Thrombomodulin (TM) stimulates angiogenesis and protects vascular endothelial cells (ECs) via its fifth epidermal growth factor-like region (TME5); however, the cell surface receptor that mediates the pro-survival signaling activated by TM has remained unknown. We applied pull-down assay followed by MALDI-TOF MS and western blot analysis, and identified G-protein coupled receptor 15 (GPR15) as a binding partner of TME5. TME5 rescued growth inhibition and apoptosis caused by calcineurin inhibitor FK506 in vascular ECs isolated from wild type (WT) C57BL/6 mice. On the other hand, TME5 failed to protect ECs isolated from GPR15 knockout (GPR15 KO) mice from FK506-caused vascular injury. TME5 induced activation of extracellular signal-regulated kinase (ERK) and increased level of anti-apoptotic proteins in a GPR15 dependent manner. In addition, in vivo Matrigel plug angiogenesis assay found that TME5 stimulated angiogenesis in mice. TME5 promoted endothelial migration in vitro. Furthermore, TME5 increased production of NO in association with activated endothelial NO synthase (eNOS) in ECs. All these pro-angiogenesis functions of TME5 were abolished by knockout of GPR15. Our findings suggest that GPR15 plays an important role in mediating cytoprotective function as well as angiogenesis of TM.
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