Figure 8.

Schematic representation of the putative link between neuroendocrine cells and the retinoic acid signalling pathway

In the upper panel, on the left side of the scheme we have represented the normal fetal lung expressing neuroendocrine products: bombesin (Bomb) and ghrelin (Grl) as well as retinoic acid receptors (RAR). On the right side of the scheme we have represented the CDH fetal lungs, which express increased (↑) levels of neuroendocrine products (Bomb and Grl) as well as RAR. On the bottom panel, we represent the RAR explants expression after modulation (agonists and antagonists) of neuroendocrine products. Focusing on isoform α, in control explants, RAR(α) expression is significantly increased (↑) and decreased (↓) with addition of agonists (full arrows, Bomb and Grl) and antagonists (dashed arrows, Bomb Ant and Grl Ant) of neuroendocrine products, respectively. Regarding CDH explants, addition of neuroendocrine products does not induce and additionally increment RAR(α) expression when compared with untreated CDH explants (=), but addition of neuroendocrine antagonists (Bomb Ant and Grl Ant) induces a significant decrease (↓) of RAR(α) expression. As a result of these findings, we propose a mechanism of interaction between bombesin and ghrelin with the retinoic acid signalling pathway through the modulation of RAR expression that seems to be working in the hypoplastic lungs.