| First Author | Londhe VA | Year | 2011 |
| Journal | Respir Res | Volume | 12 |
| Pages | 134 | PubMed ID | 21985298 |
| Mgi Jnum | J:181392 | Mgi Id | MGI:5311265 |
| Doi | 10.1186/1465-9921-12-134 | Citation | Londhe VA, et al. (2011) Conditional deletion of epithelial IKKbeta impairs alveolar formation through apoptosis and decreased VEGF expression during early mouse lung morphogenesis. Respir Res 12:134 |
| abstractText | BACKGROUND: Alveolar septation marks the beginning of the transition from the saccular to alveolar stage of lung development. Inflammation can disrupt this process and permanently impair alveolar formation resulting in alveolar hypoplasia as seen in bronchopulmonary dysplasia in preterm newborns. NF-kappaB is a transcription factor central to multiple inflammatory and developmental pathways including dorsal-ventral patterning in fruit flies; limb, mammary and submandibular gland development in mice; and branching morphogenesis in chick lungs. We have previously shown that epithelial overexpression of NF-kappaB accelerates lung maturity using transgenic mice. The purpose of this study was to test our hypothesis that targeted deletion of NF-kappaB signaling in lung epithelium would impair alveolar formation. METHODS: We generated double transgenic mice with lung epithelium-specific deletion of IKKbeta, a known activating kinase upstream of NF-kappaB, using a cre-loxP transgenic recombination strategy. Lungs of resulting progeny were analyzed at embryonic and early postnatal stages to determine specific effects on lung histology, and mRNA and protein expression of relevant lung morphoreulatory genes. Lastly, results measuring expression of the angiogenic factor, VEGF, were confirmed in vitro using a siRNA-knockdown strategy in cultured mouse lung epithelial cells. RESULTS: Our results showed that IKKbeta deletion in the lung epithelium transiently decreased alveolar type I and type II cells and myofibroblasts and delayed alveolar formation. These effects were mediated through increased alveolar type II cell apoptosis and decreased epithelial VEGF expression. CONCLUSIONS: These results suggest that epithelial NF-kappaB plays a critical role in early alveolar development possibly through regulation of VEGF. |
