| First Author | de Paepe ME | Year | 2010 |
| Journal | Pediatr Res | Volume | 68 |
| Issue | 1 | Pages | 57-62 |
| PubMed ID | 20375852 | Mgi Jnum | J:174046 |
| Mgi Id | MGI:5050812 | Doi | 10.1203/PDR.0b013e3181e084af |
| Citation | de Paepe ME, et al. (2010) Effects of Fas-ligand overexpression on alveolar type II cell growth kinetics in perinatal murine lungs. Pediatr Res 68(1):57-62 |
| abstractText | We determined the time-specific effects of FasL overexpression on perinatal alveolar type II cell growth kinetics. To achieve temporal overexpression of respiratory epithelium-specific FasL expression, tetracycline inducible CCSP-rtTA/FasL-TetOp transgenic mice were given doxycycline (Dox) from gestational d 14 (E14) to E19 (antenatal treatment group), from postnatal d 1 (P1) to P7 (postnatal group), or from E14 to P7 (combined antenatal and postnatal group). Antenatal Dox administration induced an increase of pulmonary FasL mRNA levels in double transgenic animals up to >300-fold over single transgenic littermate controls, associated with massive fetal respiratory epithelial apoptosis and excessive postnatal lethality. Although animals from the combined antenatal/postnatal Dox treatment group continued to display evidence of increased apoptosis, there was a paradoxical increase in alveolar type II cell proliferation, resulting in a net increase in type II cell density, elevated pulmonary surfactant protein C levels and improved postnatal survival. Postnatal Dox administration was also associated with increased type II cell density, although FasL up-regulation was more variable. In conclusion, these results, and our previous studies, suggest that FasL signaling has dual timing-dependent proapoptotic and proproliferative effects on postcanalicular type II cell kinetics. |
