| First Author | Ge H | Year | 2016 |
| Journal | Am J Respir Cell Mol Biol | Volume | 54 |
| Issue | 6 | Pages | 882-91 |
| PubMed ID | 26649797 | Mgi Jnum | J:251228 |
| Mgi Id | MGI:6101252 | Doi | 10.1165/rcmb.2014-0363OC |
| Citation | Ge H, et al. (2016) Increased Lung Ischemia-Reperfusion Injury in Aquaporin 1-Null Mice Is Mediated via Decreased Hypoxia-Inducible Factor 2alpha Stability. Am J Respir Cell Mol Biol 54(6):882-91 |
| abstractText | Aquaporin (AQP) 1, a water channel protein expressed widely in vascular endothelia, has been shown to regulate cell migration, angiogenesis, and organ regeneration. Even though its role in the pathogenesis of lung ischemia-reperfusion (IR) injury has been defined, the functional role of AQP1 during long-term IR resolution remains to be clarified. Here, we found that AQP1 expression was increased at late time points (7-14 d) after IR and colocalized with endothelial cell (EC) marker CD31. Compared with IR in wild-type mice, IR in Aqp1(-/-) mice had significantly enhanced leukocyte infiltration, collagen deposition, and microvascular permeability, as well as inhibited angiogenic factor expression. AQP1 knockdown repressed hypoxia-inducible factor (HIF)-2alpha protein stability. HIF-2alpha overexpression rescued the angiogenic factor expression in pulmonary microvascular ECs with AQP1 knockdown exposed to hypoxia-reoxygenation. Furthermore, AQP1 knockdown suppressed cellular viability and capillary tube formation, and enhanced permeability in pulmonary microvascular ECs, which were partly rescued by HIF-2alpha overexpression. Thus, this study demonstrates that AQP1 deficiency delays long-term IR resolution, partly through repressing angiogenesis mediated by destabilizing HIF-2alpha. These results suggest that AQP1 participates in long-term IR resolution, at least in part by promoting angiogenesis. |
