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Previous studies by others and our group have demonstrated the expression of AQP3 protein in human chorioamniotic membranes. Here, we investigated whether cyclic adenosine monophosphate (cAMP) up-regulation of aquaporin 3 (AQP3) protein expression in human amniotic epithelial cells (hAECs) is mediated by protein kinase A (PKA) dependent or independent pathway. Cells were treated with various concentrations of Forskolin, SP-cAMP, H-89 at various time intervals or optimal concentration of Forskolin in combination with H-89 in the blocking experiments. Forskolin significantly increased cAMP levels and the expression of PKA, p-CREB and AQP3. SP-cAMP had similar effects. H-89 inhibited PKA, p-CREB and AQP3 protein expression, and attenuated the stimulatory effect of Forskolin. These results show that the AQP3 protein expression in hAECs was regulated by cAMP-PKA-CREB signal pathway. A relatively short biological half life of AQP3 renders its rapid responsiveness to regulation.

Previous studies by our group as well as other researchers have found expression of Aquaporins (AQPs) 1, 3, 8, and 9 in human chorioamniotic membranes and placenta. Our previous study found that the alteration of the expression of AQPs 1, 3, 8, and 9 in placenta and fetal membranes was an adaptive response to maintain amniotic fluid homeostasis in case of abnormal amniotic fluid volume, which is likely to affect the intramembranous absorption and transport of water and solute from mother to fetus. However, the actual regulation mechanisms of intramembranous absorption and placental water flow are not yet clear, making it difficult to treat abnormal amniotic fluid volume effectively. Several studies found that many factors, including hormone levels, osmotic pressure, temperature, and oxygen concentration, regulate expression of AQPs in placenta, fetal membranes, and other mammalian organs through several signal transduction pathways, such as the cAMP, the MAPK, the PI3K/AKT, and the PKC pathways. These factors could provide potential therapeutic targets for the treatment of abnormal amniotic fluid volume.