| First Author | Tanaka A | Year | 2010 |
| Journal | Blood | Volume | 115 |
| Issue | 20 | Pages | 4138-47 |
| PubMed ID | 20231428 | Mgi Jnum | J:160230 |
| Mgi Id | MGI:4453908 | Doi | 10.1182/blood-2009-05-223057 |
| Citation | Tanaka A, et al. (2010) Inhibition of endothelial cell activation by bHLH protein E2-2 and its impairment of angiogenesis. Blood 115(20):4138-47 |
| abstractText | E2-2 belongs to the basic helix-loop-helix (bHLH) family of transcription factors. E2-2 associates with inhibitor of DNA binding (Id) 1, which is involved in angiogenesis. In this paper, we demonstrate that E2-2 interacts with Id1 and provide evidence that this interaction potentiates angiogenesis. Mutational analysis revealed that the HLH domain of E2-2 is required for the interaction with Id1 and vice versa. In addition, Id1 interfered with E2-2-mediated effects on luciferase reporter activities. Interestingly, injection of E2-2-expressing adenoviruses into Matrigel plugs implanted under the skin blocked in vivo angiogenesis. In contrast, the injection of Id1-expressing adenoviruses rescued E2-2-mediated inhibition of in vivo angiogenic reaction. Consistent with the results of the Matrigel plug assay, E2-2 could inhibit endothelial cell (EC) migration, network formation, and proliferation. On the other hand, knockdown of E2-2 in ECs increased EC migration. The blockade of EC migration by E2-2 was relieved by exogenous expression of Id1. We also demonstrated that E2-2 can perturb VEGFR2 expression via inhibition of VEGFR2 promoter activity. This study suggests that E2-2 can maintain EC quiescence and that Id1 can counter this effect. |
