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.
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http://dx.doi.org/10.1016/j.jpedsurg.2005.03.022 | DOI Listing |
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