Fibroblast growth factor 2 (FGF2 or basic FGF) regulates a wide range of cell biological functions including proliferation, angiogenesis, migration, differentiation, and injury repair. However, the roles of FGF2 and the underlying mechanisms of action in influenza A virus (IAV)-induced lung injury remain largely unexplored. In this study, we report that microRNA-194-5p (miR-194) expression is significantly decreased in A549 alveolar epithelial cells (AECs) following infection with IAV/Beijing/501/2009 (BJ501). We found that miR-194 can directly target FGF2, a novel antiviral regulator, to suppress FGF2 expression at the mRNA and protein levels. Overexpression of miR-194 facilitated IAV replication by negatively regulating type I interferon (IFN) production, whereas reintroduction of FGF2 abrogated the miR-194-induced effects on IAV replication. Conversely, inhibition of miR-194 alleviated IAV-induced lung injury by promoting type I IFN antiviral activities in vivo. Importantly, FGF2 activated the retinoic acid-inducible gene I signaling pathway, whereas miR-194 suppressed the phosphorylation of tank binding kinase 1 and IFN regulatory factor 3. Our findings suggest that the miR-194-FGF2 axis plays a vital role in IAV-induced lung injury, and miR-194 antagonism might be a potential therapeutic target during IAV infection.

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retinoic acidinducible gene i signaling fgf2 inhibition of mir194 alleviated iavinduced lung injury a549 alveolar epithelial mir194fgf2 axis type i interferon ifn iav replication cell biological functions proliferation angiogenesis migration differentiation and injury tank binding kinase microrna1945p mir194 ifn regulatory factor regulator ifn antiviral activities

Keyu Wang,Chengcai Lai,Hongjing Gu,Lingna Zhao,Min Xia,Penghui Yang,Penghui Yang,Xiliang Wang,.miR-194 Inhibits Innate Antiviral Immunity by Targeting FGF2 in Influenza H1N1 Virus Infection. 8 (),.

Keyu Wang,Chengcai Lai,Hongjing Gu,Lingna Zhao,Min Xia,Penghui Yang,Penghui Yang,Xiliang Wang,"miR-194 Inhibits Innate Antiviral Immunity by Targeting FGF2 in Influenza H1N1 Virus Infection" 8

Keyu Wang,Chengcai Lai,Hongjing Gu,Lingna Zhao,Min Xia,Penghui Yang,Penghui Yang,Xiliang Wang,"miR-194 Inhibits Innate Antiviral Immunity by Targeting FGF2 in Influenza H1N1 Virus Infection"