Spatial and temporal patterns of c-kit positive cells in embryonic lungs.

BACKGROUND: It has been reported that the smooth muscles in fetal airways exhibit spontaneous phasic contractions throughout gestation. However, the mechanism of these spontaneous contractions is unknown. In the bowel wall, interstitial cells of Cajal (ICCs), which are derived from c-kit positive precursor cells, play an important role as pacemaker cells responsible for the spontaneous, rhythmic activity in the smooth muscle cells. In this study, we investigated the spatial and temporal expression patterns of c-kit positive cells in the embryonic lung and its relationship to the smooth muscle cells surrounding the trachea and the bronchus. METHODS: Rat fetuses were removed from timed pregnant dams on embryonic days (E) 11.5, 13.5, 15.5, and 17.5. Immunohistochemical studies with anti c-kit antibody and anti α-SMA antibody were carried out using frozen sections. RESULTS: A small number of c-kit positive cells were observed in the mesenchyme of the lung bud on day E 11.5. They were markedly increased in number on day E 13.5. On day E 15.5 and on day E 17.5, strong c-kit expressions were observed on the vascular wall and moderate expressions in the mesenchyme. C-kit positive cells co-localized with α-SMA positive smooth muscle cells surrounding the airway epithelium. CONCLUSION: Co-localization of c-kit positive cells and airway smooth muscles in the fetal lung suggests that c-kit positive cells may play an important role in the spontaneous contractions of fetal airways. C-kit expressions in the fetal pulmonary vascular wall suggest that these cells may play an important role in vasculogenesis and angiogenesis of the embryonic lung.

Effect of nitric oxide on fibroblast growth factor-10 and bone morphogenetic protein 4 expressions in the branching morphogenesis of fetal rat lung explants.

PURPOSE: Nitric oxide (NO) can accelerate branching morphogenesis of fetal rat lung explants in vitro, whereas its exact mechanism remains unclear. In this study, we investigate the effect of NO on the expression of fibroblast growth factor-10 (FGF10) and bone morphogenetic protein-4 (BMP4), which plays an important role in bud formation. METHODS: Fetal rat lungs harvested on day 13.5 of gestation were cultured in serum-free medium for 72 hours with 0, 50, 100, and 200 micromol/L of an NO donor, DETA NONOate (DETA/NO) (n = 4, 3, 6, and 5). The ratio of bud increment of each cultured lung was calculated, and the FGF10 and BMP4 mRNA expression levels were analyzed by real-time reverse transcription polymerase chain reaction. RESULTS: Bud increment ratio was significantly increased in 50, 100, and 200 micromol/L DETA/NO (3.3 +/- 0.2, 3.0 +/- 0.3, and 3.5 +/- 0.5) compared to controls (1.9 +/- 0.3) (P < .05). There was a significant increase in BMP4 mRNA expression in 100 micromol/L DETA/NO (190% +/- 20%) compared to controls (100% +/- 30%) (P < .05), whereas FGF10 mRNA expression was not significantly different between each DETA/NO group and controls. CONCLUSION: The NO donor not only promotes branching of fetal lung explants but also upregulates expression of BMP4, which is an important regulator of branching morphogenesis.