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. 2016 Jun 3;7:147. doi: 10.3389/fphar.2016.00147

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Copyright © 2016 Ghisalberti, Borzì, Cetrullo, Flamigni and Cairo.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Exogenous spermidine may interrupt the vicious cycling in chronic airways diseases. Locally delivered spermidine works both as a TCPTP agonist and stimulator of the expression of genes coding for adherens and tight junction proteins. The former effect down-regulates the secondary growth factor signaling pathways, such as epidermal growth factor (EGF) and transforming growth factor-β (TGF-β) receptors and relevant pathways. This repression prevents the epithelial-to-mesenchymal transition to occur, which would further impair the epithelial impermeability and contribute to chronic remodeling and fibrosis. Strengthening the airways epithelial barrier translates into a reduced exposure to allergens, stressor proteins, and reactive oxygen species.