| First Author | Olave N | Year | 2012 |
| Journal | Am J Physiol Lung Cell Mol Physiol | Volume | 302 |
| Issue | 9 | Pages | L857-65 |
| PubMed ID | 22287612 | Mgi Jnum | J:187497 |
| Mgi Id | MGI:5437199 | Doi | 10.1152/ajplung.00258.2011 |
| Citation | Olave N, et al. (2012) Transforming growth factor-beta regulates endothelin-1 signaling in the newborn mouse lung during hypoxia exposure. Am J Physiol Lung Cell Mol Physiol 302(9):L857-65 |
| abstractText | We have previously shown that inhibition of transforming growth factor-beta (TGF-beta) signaling attenuates hypoxia-induced inhibition of alveolar development and abnormal pulmonary vascular remodeling in the newborn mice and that endothelin-A receptor (ETAR) antagonists prevent and reverse the vascular remodeling. The current study tested the hypothesis that inhibition of TGF-beta signaling attenuates endothelin-1 (ET-1) expression and thereby reduces effects of hypoxia on the newborn lung. C57BL/6 mice were exposed from birth to 2 wk of age to either air or hypoxia (12% O(2)) while being given either BQ610 (ETAR antagonist), BQ788 (ETBR antagonist), 1D11 (TGF-beta neutralizing antibody), or vehicle. Lung function and development and TGF-beta and ET-1 synthesis were assessed. Hypoxia inhibited alveolar development, decreased lung compliance, and increased lung resistance. These effects were associated with increased TGF-beta synthesis and signaling and increased ET-1 synthesis. BQ610 (but not BQ788) improved lung function, without altering alveolar development or increased TGF-beta signaling in hypoxia-exposed animals. Inhibition of TGF-beta signaling reduced ET-1 in vivo, which was confirmed in vitro in mouse pulmonary endothelial, fibroblast, and epithelial cells. ETAR blockade improves function but not development of the hypoxic newborn lung. Reduction of ET-1 via inhibition of TGF-beta signaling indicates that TGF-beta is upstream of ET-1 during hypoxia-induced signaling in the newborn lung. |
