| First Author | Ren B | Year | 2010 |
| Journal | J Clin Invest | Volume | 120 |
| Issue | 4 | Pages | 1217-28 |
| PubMed ID | 20237411 | Mgi Jnum | J:159682 |
| Mgi Id | MGI:4452269 | Doi | 10.1172/JCI39837 |
| Citation | Ren B, et al. (2010) ERK1/2-Akt1 crosstalk regulates arteriogenesis in mice and zebrafish. J Clin Invest 120(4):1217-28 |
| abstractText | Arterial morphogenesis is an important and poorly understood process. In particular, the signaling events controlling arterial formation have not been established. We evaluated whether alterations in the balance between ERK1/2 and PI3K signaling pathways could stimulate arterial formation in the setting of defective arterial morphogenesis in mice and zebrafish. Increased ERK1/2 activity in mouse ECs with reduced VEGF responsiveness was achieved in vitro and in vivo by downregulating PI3K activity, suppressing Akt1 but not Akt2 expression, or introducing a constitutively active ERK1/2 construct. Such restoration of ERK1/2 activation was sufficient to restore impaired arterial development and branching morphogenesis in synectin-deficient mice and synectin-knockdown zebrafish. The same approach effectively stimulated arterial growth in adult mice, restoring arteriogenesis in mice lacking synectin and in atherosclerotic mice lacking both LDL-R and ApoB48. We therefore conclude that PI3K-ERK1/2 crosstalk plays a key role in the regulation of arterial growth and that the augmentation of ERK signaling via suppression of the PI3K signaling pathway can effectively stimulate arteriogenesis. |
