| First Author | Nyp MF | Year | 2018 |
| Journal | Physiol Rep | Volume | 6 |
| Issue | 5 | PubMed ID | 29484847 |
| Mgi Jnum | J:274162 | Mgi Id | MGI:6296559 |
| Doi | 10.14814/phy2.13585 | Citation | Nyp MF, et al. (2018) Lung epithelial-specific TRIP-1 overexpression maintains epithelial integrity during hyperoxia exposure. Physiol Rep 6(5) |
| abstractText | The onset and degree of injury occurring in animals that develop hyperoxic acute lung injury (HALI) is dependent on age at exposure, suggesting that developmentally regulated pathways/factors must underlie initiation of the epithelial injury and subsequent repair. Type II TGFbeta receptor interacting protein-1 (TRIP-1) is a negative regulator of TGFbeta signaling, which we have previously shown is a developmentally regulated protein with modulatory effects on epithelial-fibroblastic signaling. The aim of this study was to assess if type II alveolar epithelial cells overexpressing TRIP-1 are protected against hyperoxia-induced epithelial injury, and in turn HALI. Rat lung epithelial cells (RLE) overexpressing TRIP-1 or LacZ were exposed to 85% oxygen for 4 days. A surfactant protein C (SPC)-driven TRIP-1 overexpression mouse (TRIP-1(AECTg+) ) was generated and exposed to hyperoxia (>95% for 4 days) at 4 weeks of age to assess the effects TRIP-1 overexpression has on HALI. RLE overexpressing TRIP-1 resisted hyperoxia-induced apoptosis. Mice overexpressing TRIP-1 in their lung type II alveolar epithelial cells (TRIP-1(AECTg+) ) showed normal lung development, increased phospho-AKT level and E-cadherin, along with resistance to HALI, as evidence by less TGFbeta activation, apoptosis, alveolar macrophage influx, KC expression. Taken together, these findings point to existence of a TRIP-1 mediated molecular pathway affording protection against epithelial/acute lung injury. |
