ANP/NPRA Inhibits Epithelial-Mesenchymal Transition of Airway by Targeting Smad3 in Asthma

Atrial natriuretic peptide (ANP) has a protective effect on allergic disorders of airway. It could inhibit transforming growth factor beta 1 (TGF-β1)-induced epithelial-mesenchymal transition (EMT) of human airway cells. In this study, we investigated the role and mechanism of ANP in airway EMT with asthma. Asthma model was established with BALB/c mice using ovalbumin. Asthmatic mice were respectively treated with ANP, NPRA antagonist (A71915) or ANP+A71915. The protein expressions of TGF-β1, ANP, epithelial cadherin (E-Cadherin), α-smooth muscle actin (α-SMA), Smad3 and phosphorylated-Smad3 in lung tissues were detected by immunohistochemistry and Western blotting. The mRNA expressions of E-Cadherin, α-SMA, Smad3 in lung tissues were measured using real-time PCR. The levels of TGF-β1, IL-4 and IL-5 in bronchoalveolar lavage fluid, cyclic guanosine monophosphate (cGMP) in lung tissues, and ANP in serum were assessed by ELISA. Compared with controls, mRNA and protein expressions of E-Cadherin were decreased, whereas α-SMA were increased in asthma group, which could be reversed by ANP. cGMP level was higher in ANP group than asthma group, whereas p-Smad3 expression was lower. TGF-β1, IL-4 and IL-5 levels were higher in asthma group than controls, which could be reversed by ANP. The effect of ANP in asthma group could be inhibited by A71915. Therefore, in asthma, ANP/NPRA could inhibit airway EMT by targeting Smad3 via attenuating phosphorylation of Smad3. cGMP signaling may be involved into this process. This may provide a potential of ANP in treatment on refractory asthma with airway remodeling.