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H1N1 Influenza Virus Cross-Activates Gli1 to Disrupt the Intercellular Junctions of Alveolar Epithelial Cells.
Cell Reports ( IF 7.5 ) Pub Date : 2020-06-30 , DOI: 10.1016/j.celrep.2020.107801
Tao Ruan 1 , Jing Sun 2 , Wei Liu 2 , Richard A Prinz 3 , Daxin Peng 4 , Xiufan Liu 4 , Xiulong Xu 5
Affiliation  

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.



中文翻译:

H1N1流感病毒交叉激活Gli1,破坏肺泡上皮细胞的细胞间连接。

甲型流感病毒(IAV)主要感染气道和肺泡上皮细胞并破坏细胞间连接,导致细胞旁通透性增加。尽管这种病理变化在肺组织损伤和继发感染中起关键作用,但是IAV诱导的肺泡屏障损害的分子机制仍然不清楚。在这里,我们报告说,Gli1,在声波刺猬(Shh)信号传导途径中的转录因子,在H1N1病毒(PR8)感染的A549细胞和H1N1病毒感染的肺部中被MAP和PI3激酶途径交叉激活老鼠。Gli1激活诱导Snail表达,从而下调包括E-cadherin,ZO-1和Occludin在内的细胞间连接蛋白的表达,并增加细胞旁通透性。抑制Shh通路可恢复感染H1N1的细胞中Snail和细胞间连接蛋白的水平。我们的研究表明,Gli1激活在破坏细胞间连接和促进H1N1病毒感染的发病机理中起着重要作用。

更新日期:2020-06-30
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