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.
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This work was supported by grants from the National Natural Science Foundation of China (Nos. 81360006, 81560007 and 81760009), the Guangxi Natural Science Foundation (No. 2015GXNSFAA139106), and the Education Department of Hunan Province (No. 16C1404). The funding sources had no involvement into this study.
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Conflict of interest
All authors declare that they have no conflict of interest.
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