| First Author | Liu G | Year | 2014 |
| Journal | Sci Rep | Volume | 4 |
| Pages | 5543 | PubMed ID | 24986487 |
| Mgi Jnum | J:251161 | Mgi Id | MGI:6102680 |
| Doi | 10.1038/srep05543 | Citation | Liu G, et al. (2014) NF-kappaB-to-AP-1 switch: a mechanism regulating transition from endothelial barrier injury to repair in endotoxemic mice. Sci Rep 4:5543 |
| abstractText | Endothelial barrier disruption is a hallmark of multiple organ injury (MOI). However, mechanisms governing the restoration of endothelial barrier function are poorly understood. Here, we uncovered an NF-kappaB-to-AP-1 switch that regulates the transition from barrier injury to repair following endotoxemic MOI. Endothelial NF-kappaB mediates barrier repair by inhibiting endothelial cell (EC) apoptosis. Blockade of endothelial NF-kappaB pathway activated the activator protein (AP)-1 pathway (NF-kappaB-to-AP-1 switch), which compensated for the anti-apoptotic and barrier-repair functions of NF-kappaB. The NF-kappaB-to-AP-1 switch occurred at 24 hours (injury to repair transition phase), but not at 48 hours (repair phase) post-LPS, and required an inflammatory signal within the endothelium. In the absence of an inflammatory signal, the NF-kappaB-to-AP-1 switch failed, resulting in enhanced EC apoptosis, augmented endothelial permeability, and impeded transition from barrier injury to recovery. The NF-kappaB-to-AP-1 switch is a protective mechanism to ensure timely transition from endothelial barrier injury to repair, accelerating barrier restoration following MOI. |
