AI Article Synopsis
- Thrombomodulin's fifth region (TME5) enhances blood vessel formation (angiogenesis) and protects blood vessel cells (endothelial cells) from damage caused by specific drugs.
- Researchers identified GPR15, a G-protein coupled receptor, as the crucial protein that interacts with TME5 to activate protective signaling in these endothelial cells.
- The study demonstrated that TME5's protective and angiogenic benefits are significantly diminished when GPR15 is absent, highlighting GPR15's essential role in mediating these effects.
Article 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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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5429650 | PMC |
| http://dx.doi.org/10.1038/s41598-017-00781-w | DOI Listing |
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