| First Author | Qiu C | Year | 2017 |
| Journal | Nat Commun | Volume | 8 |
| Pages | 15426 | PubMed ID | 28569748 |
| Mgi Jnum | J:249574 | Mgi Id | MGI:5921332 |
| Doi | 10.1038/ncomms15426 | Citation | Qiu C, et al. (2017) The critical role of SENP1-mediated GATA2 deSUMOylation in promoting endothelial activation in graft arteriosclerosis. Nat Commun 8:15426 |
| abstractText | Data from clinical research and our previous study have suggested the potential involvement of SENP1, the major protease of post-translational SUMOylation, in cardiovascular disorders. Here, we investigate the role of SENP1-mediated SUMOylation in graft arteriosclerosis (GA), the major cause of allograft failure. We observe an endothelial-specific induction of SENP1 and GATA2 in clinical graft rejection specimens that show endothelial activation-mediated vascular remodelling. In mouse aorta transplantation GA models, endothelial-specific SENP1 knockout grafts demonstrate limited neointima formation with attenuated leukocyte recruitment, resulting from diminished induction of adhesion molecules in the graft endothelium due to increased GATA2 SUMOylation. Mechanistically, inflammation-induced SENP1 promotes the deSUMOylation of GATA2 and IkappaBalpha in endothelial cells, resulting in increased GATA2 stability, promoter-binding capability and NF-kappaB activity, which leads to augmented endothelial activation and inflammation. Therefore, upon inflammation, endothelial SENP1-mediated SUMOylation drives GA by regulating the synergistic effect of GATA2 and NF-kappaB and consequent endothelial dysfunction. |
