| First Author | Ikegami M | Year | 2008 |
| Journal | J Appl Physiol (1985) | Volume | 104 |
| Issue | 6 | Pages | 1753-60 |
| PubMed ID | 18369093 | Mgi Jnum | J:183960 |
| Mgi Id | MGI:5319603 | Doi | 10.1152/japplphysiol.00875.2007 |
| Citation | Ikegami M, et al. (2008) STAT-3 regulates surfactant phospholipid homeostasis in normal lung and during endotoxin-mediated lung injury. J Appl Physiol 104(6):1753-60 |
| abstractText | Acute lung injury associated with surfactant deficiency remains a major cause of pulmonary morbidity and mortality. Since signal transducer and activator of transcription-3 (STAT-3) plays an important role in protecting respiratory epithelial cells during injury, we hypothesized that STAT-3 may regulate gene expression in type II cells that mediate surfactant phospholipid synthesis. Conditional deletion of Stat-3 in respiratory epithelial cells in the lung of transgenic mice (Stat-3(Delta/Delta) mice) decreased surfactant phospholipid synthesis and secretion. Deletion of Stat-3 was associated with decreased expression of Akt2, Srebf-1, and other genes expressed in type II cells that may influence surfactant phospholipid synthesis (Glut-1, Slc34a2, Gpam, Acox2, and Cds2). Stat-3(Delta/Delta) mice were more susceptible to intratracheal lipopolysaccharide (LPS). Saturated phosphatidylcholine and surfactant protein B levels were significantly decreased in bronchoalveolar lavage fluid from LPS-treated Stat-3(Delta/Delta) mice. Alveolar capillary leak, proinflammatory cytokine expression, and perturbations of lung mechanics caused by LPS were exacerbated after deletion of STAT-3. STAT-3 plays a critical role in the regulation of surfactant lipid synthesis in the normal lung and during lung injury caused by LPS. |
