| First Author | Zhang Y | Year | 2013 |
| Journal | FASEB J | Volume | 27 |
| Issue | 10 | Pages | 4041-58 |
| PubMed ID | 23771928 | Mgi Jnum | J:201177 |
| Mgi Id | MGI:5511115 | Doi | 10.1096/fj.13-231225 |
| Citation | Zhang Y, et al. (2013) Lung endothelial HO-1 targeting in vivo using lentiviral miRNA regulates apoptosis and autophagy during oxidant injury. FASEB J 27(10):4041-4058 |
| abstractText | The lung endothelium is a major target for inflammatory and oxidative stress. Heme oxygenase-1 (HO-1) induction is a crucial defense mechanism during oxidant challenges, such as hyperoxia. The role of lung endothelial HO-1during hyperoxia in vivo is not well defined. We engineered lentiviral vectors with microRNA (miRNA) sequences controlled by vascular endothelium cadherin (VE-cad) to study the specific role of lung endothelial HO-1. Wild-type (WT) murine lung endothelial cells (MLECs) or WT mice were treated with lentivirus and exposed to hyperoxia (95% oxygen). We detected HO-1 knockdown ( approximately 55%) specifically in the lung endothelium. MLECs and lungs showed approximately a 2-fold increase in apoptosis and ROS generation after HO-1 silencing. We also demonstrate for the first time that silencing endothelial HO-1 has the same effect on lung injury and survival as silencing HO-1 in multiple lung cell types and that HO-1 regulates caspase 3 activation and autophagy in endothelium during hyperoxia. These studies demonstrate the utility of endothelial-targeted gene silencing in vivo using lentiviral miRNA constructs to assess gene function and that endothelial HO-1 is an important determinant of survival during hyperoxia.-Zhang, Y., Jiang, G., Sauler, M., Lee, P. J. Lung endothelial HO-1 targeting in vivo using lentiviral miRNA regulates apoptosis and autophagy during oxidant injury. |
