Dobutamine Up-Regulates Aquaporin 5 Expression In Septic Pulmonary Edema Model & It;In Vitro & It; Via Camp-Pka/Creb Signaling Pathway

Acute pulmonary edema is one of the most common complications of sepsis. Dobutamine is a beta-adrenalin receptor agonist that has been proved to reduce pulmonary edema by increasing the expression of aquaporin 5 (AQP5). However, the molecular mechanisms involved are still unclear. The present study aimed at investigating the effect of dobutamine on the expression of AQP5 during septic pulmonary edema, and also whether the cAMP-PKA/CREB signaling pathway is involved. A549 cells were exposed to LPS in an in vitro study, to establish sepsis cell model. The cells were then treated with dobutamine, 8-Br-cAMP, which is the inhibitor of beta-adrenalin receptor (ICI 118, 551) and PKA inhibitor H-89. Moreover, cell morphology, cell activity, cAMP level and mRNA and protein expression of related genes were also analyzed in this study. Results from this study demonstrated that the volume of cells was smaller than in the control group, and the cell activity decreased when the cells were treated with LPS. Moreover, the cAMP level and expression of AQP5, PKA alpha cat and p-CREB on mRNA and protein also decreased. Nevertheless, these changes were reversed by dobutamine and 8-Br-cAMP in different degrees. The effects of ICI 118,551 and H-89 treatments were similar to LPS treatment, and cell activity, cAMP level and mRNA and protein expressions levels for AQP5, PKA alpha cat and p-CREB deoreased obviously when treated with ICI 118,551 and H-89. This study demonstrated that the dobutamine contributed to a significantly increased AQP5 expression in the pulmonary edema cell model. Moreover, the cAMP-PKA/CREB signaling pathway plays an important role in AQP5 regulation. Therefore, these findings will provide new ideas on methods for regulating the expression of AQP5 in the treatment of septic pulmonary edema.