H1N1 Influenza Virus Cross-Activates Gli1 to Disrupt the Intercellular Junctions of Alveolar Epithelial Cells.
A549 Cells
Alveolar Epithelial Cells
/ drug effects
Animals
Dogs
Humans
Influenza A Virus, H1N1 Subtype
/ drug effects
Intercellular Junctions
/ drug effects
Lung
/ metabolism
Madin Darby Canine Kidney Cells
Mice, Inbred C57BL
Mitogen-Activated Protein Kinases
/ metabolism
Models, Biological
Phosphatidylinositol 3-Kinases
/ metabolism
Proto-Oncogene Proteins c-akt
/ metabolism
Pyridines
/ pharmacology
Pyrimidines
/ pharmacology
Signal Transduction
/ drug effects
Snail Family Transcription Factors
/ metabolism
Zinc Finger Protein GLI1
/ metabolism
E-cadherin
Gli1
MAP kinase
Occludin
PI3 kinase
Snail
ZO-1
epithelial junctions
influenza A virus
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
30 06 2020
30 06 2020
Historique:
received:
01
08
2019
revised:
26
11
2019
accepted:
01
06
2020
entrez:
2
7
2020
pubmed:
2
7
2020
medline:
29
4
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32610119
pii: S2211-1247(20)30782-8
doi: 10.1016/j.celrep.2020.107801
pii:
doi:
Substances chimiques
GANT 61
0
Pyridines
0
Pyrimidines
0
Snail Family Transcription Factors
0
Zinc Finger Protein GLI1
0
Proto-Oncogene Proteins c-akt
EC 2.7.11.1
Mitogen-Activated Protein Kinases
EC 2.7.11.24
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
107801Informations de copyright
Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests The authors declare no competing interests.