| First Author | Ren R | Year | 2007 |
| Journal | Blood | Volume | 109 |
| Issue | 7 | Pages | 2847-53 |
| PubMed ID | 17119124 | Mgi Jnum | J:145352 |
| Mgi Id | MGI:3834337 | Doi | 10.1182/blood-2006-08-039743 |
| Citation | Ren R, et al. (2007) Gene expression profiles identify a role for cyclooxygenase 2-dependent prostanoid generation in BMP6-induced angiogenic responses. Blood 109(7):2847-53 |
| abstractText | The bone morphogenetic protein (BMP) family of proteins participates in regulation of angiogenesis in physiologic and pathologic conditions. To investigate the molecular mechanisms that contribute to BMP-dependent angiogenic signaling, we performed gene expression profiling of BMP6-treated mouse endothelial cells. We detected 77 mRNAs that were differentially regulated after BMP6 stimulation. Of these, cyclooxygenase 2 (Cox2) was among the most highly up-regulated by BMP stimulation, suggesting a role for Cox2 as a downstream regulator of BMP-induced angiogenesis. Up-regulation of Cox2 by BMP6 was detected at both mRNA and protein levels in endothelial cells, and BMP6 increased production of prostaglandins in a Cox2-dependent fashion. BMP6 up-regulated Cox2 at the transcriptional level through upstream SMAD-binding sites in the Cox2 promoter. Pharmacologic inhibition of Cox2, but not Cox1, blocked BMP6-induced endothelial cell proliferation, migration, and network assembly. BMP6-dependent microvessel outgrowth was markedly attenuated in aortic rings from Cox2-/- mice or after pharmacologic inhibition of Cox2 in aortas from wild-type mice. These results support a necessary role for Cox2 in mediating proangiogenic activities of BMP6. These data indicate that Cox2 may serve as a unifying component downstream from disparate pathways to modulate angiogenic responses in diseases in which neovascularization plays an underlying pathophysiologic role. |
