tetano
Editor, Senior Moderator
Cell Rep
. 2020 Jun 30;31(13):107801.
doi: 10.1016/j.celrep.2020.107801.
H1N1 Influenza Virus Cross-Activates Gli1 to Disrupt the Intercellular Junctions of Alveolar Epithelial Cells
Tao Ruan[SUP] 1 [/SUP], Jing Sun[SUP] 2 [/SUP], Wei Liu[SUP] 2 [/SUP], Richard A Prinz[SUP] 3 [/SUP], Daxin Peng[SUP] 4 [/SUP], Xiufan Liu[SUP] 4 [/SUP], Xiulong Xu[SUP] 5 [/SUP]
Affiliations
Abstract
Influenza A virus (IAV) primarily infects the airway and alveolar epithelial cells and disrupts the intercellular junctions, leading to increased paracellular permeability. Although this pathological change plays a critical role in lung tissue injury and secondary infection, the molecular mechanism of IAV-induced damage to the alveolar barrier remains obscure. Here, we report that Gli1, a transcription factor in the sonic hedgehog (Shh) signaling pathway, is cross-activated by the MAP and PI3 kinase pathways in H1N1 virus (PR8)-infected A549 cells and in the lungs of H1N1 virus-infected mice. Gli1 activation induces Snail expression, which downregulates the expression of intercellular junction proteins, including E-cadherin, ZO-1, and Occludin, and increases paracellular permeability. Inhibition of the Shh pathway restores the levels of Snail and intercellular junction proteins in H1N1-infected cells. Our study suggests that Gli1 activation plays an important role in disrupting the intercellular junctions and in promoting the pathogenesis of H1N1 virus infections.
Keywords: E-cadherin; Gli1; MAP kinase; Occludin; PI3 kinase; Snail; ZO-1; epithelial junctions; influenza A virus.
. 2020 Jun 30;31(13):107801.
doi: 10.1016/j.celrep.2020.107801.
H1N1 Influenza Virus Cross-Activates Gli1 to Disrupt the Intercellular Junctions of Alveolar Epithelial Cells
Tao Ruan[SUP] 1 [/SUP], Jing Sun[SUP] 2 [/SUP], Wei Liu[SUP] 2 [/SUP], Richard A Prinz[SUP] 3 [/SUP], Daxin Peng[SUP] 4 [/SUP], Xiufan Liu[SUP] 4 [/SUP], Xiulong Xu[SUP] 5 [/SUP]
Affiliations
- PMID: 32610119
- DOI: 10.1016/j.celrep.2020.107801
Abstract
Influenza A virus (IAV) primarily infects the airway and alveolar epithelial cells and disrupts the intercellular junctions, leading to increased paracellular permeability. Although this pathological change plays a critical role in lung tissue injury and secondary infection, the molecular mechanism of IAV-induced damage to the alveolar barrier remains obscure. Here, we report that Gli1, a transcription factor in the sonic hedgehog (Shh) signaling pathway, is cross-activated by the MAP and PI3 kinase pathways in H1N1 virus (PR8)-infected A549 cells and in the lungs of H1N1 virus-infected mice. Gli1 activation induces Snail expression, which downregulates the expression of intercellular junction proteins, including E-cadherin, ZO-1, and Occludin, and increases paracellular permeability. Inhibition of the Shh pathway restores the levels of Snail and intercellular junction proteins in H1N1-infected cells. Our study suggests that Gli1 activation plays an important role in disrupting the intercellular junctions and in promoting the pathogenesis of H1N1 virus infections.
Keywords: E-cadherin; Gli1; MAP kinase; Occludin; PI3 kinase; Snail; ZO-1; epithelial junctions; influenza A virus.