Influenza A/WSN/33 virus regulates the expression of orosomucoid through STAT3 phosphorylation mediated by TGF-β1/Smad3

Abstract:

Objective To investigate the regulatory effect of transforming growth factor-beta 1 (TGF-β1)/Smad3 on orosomucoid (ORM) expression during infection with influenza A/WSN/33 virus (hereinafter referred to as WSN).Methods A549 cells were either infected with WSN or treated with TGF-β1, followed by treatment with Smad3 inhibitors. The mRNA levels of ORMs were assessed by RT-PCR. Subsequently, cell lines with signal transducer and activator of transcription 3 (STAT3) overexpression and knockdown were established, and RT-PCR and Western blotting were employed to evaluate the impact of STAT3 on ORM expression induced by the influenza virus. Furthermore, A549 cells underwent treatment with TGF-β1, after which the phosphorylation status of STAT3 was analyzed via Western blotting. Finally, the phosphorylation level of STAT3 was detected after inhibiting the activity of Smad3 or knocking down the expression of Smad3 in A549 cells infected with WSN or treated with TGF-β1.Results TGF-β1 regulated the expression of ORM1 and ORM2 through the activation of Smad3, a key mediator in the TGF-β signaling pathway. Concurrently, STAT3 was implicated in modulating ORM1 and ORM2 expression during WSN infection. Additionally, TGF-β1 was shown to induce STAT3 phosphorylation. Notably, inhibiting Smad3 activation or knocking down Smad3 expression suppressed STAT3 phosphorylation.Conclusion The regulation of ORM1 and ORM2 expression by WSN relied on STAT3 phosphorylation mediated by TGF-β1/Smad3.