SHORT-TERM RESPONSE TO TRACHEAL OCCLUSION DURING PERINATAL LUNG DEVELOPMENT IN MICE

Abstract

Tracheal occlusion (TO) is known to stimulate lung growth. The aim of this research is to investigate early cellular responses to TO during perinatal growth in order to identify cellular targets in fetal mouse lungs that respond rapidly to surgically induced stretch. TO, or sham-TO, surgery was performed at 16.5 gestational days in fetal mice. Cellular activation, proliferation, and apoptosis were assessed on lung tissue sections harvested at various time points within the first 24 hours after the surgery. Lung tissue from unoperated fetuses and newborn mice served as controls to establish the pattern of cellular proliferation and apoptosis during normal lung development. When compared with sham-TO, TO induces a significantly higher expression of pulmonary c-Fos mRNA within 1 hour after surgery. When compared with sham-TO and unoperated controls, TO induces a rapid (1-hour) increase in proliferating cell nuclear antigen (PCNA) expression within differentiated epithelial airways. In contrast, a significant increase in the apoptotic index of mesenchymal cells from TO lungs was not observed before 24 hours when compared with sham-TO and controls. The data demonstrate that in vivo TO induces an immediate cellular response and that stretch both primarily and significantly accelerates epithelial cell proliferation and mesenchymal cell apoptosis. Moreover, we conclude that TO reduces the gestational time required to reach the natural peaks of proliferation and apoptosis associated with normal lung development, thus resulting in an apparent stimulation of lung growth.