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Download 20170117-Syndecan-1 Attenuates Lung Injury during Influenza Infection.pdf
Judul Syndecan-1 Attenuates Lung Injury during Influenza Infection by Potentiating c-Met Signaling to Suppress Epithelial Apoptosis
Abstract Abstract
Rationale: Syndecan-1 is a cell surface heparan sulfate
proteoglycan primarily expressed in the lung epithelium.
Because the influenza virus is tropic to the airway
epithelium, we investigated the role of syndecan-1 in
influenza infection.
Objectives: To determine the mechanism by which
syndecan-1 regulates the lung mucosal response to influenza
infection.
Methods: Wild-type (WT) and Sdc12/2 mice were infected with
a H1N1 virus (PR8) as an experimental model of influenza
infection. Human and murine airway epithelial cell cultures
were also infected with PR8 to study the mechanism by
which syndecan-1 regulates the inflammatory response.
Measurement and Main Results:We found worsened outcomes
andlung injury inSdc12/2mice compared withWTmice after influenza
infection. Our data demonstrated that syndecan-1 suppresses bronchial
epithelial apoptosis during influenza infection to limit widespread lung
inflammation. Furthermore, we determined that syndecan-1 attenuated
apoptosis by crosstalking with c-Met to potentiate its cytoprotective
signals in airway epithelial cells during influenza infection.
Conclusions: Our work shows that cell-associated syndecan-1 has an
important role in regulating lung injury.Ourfindings demonstrate anovel
mechanism in which cell membrane‚Äďassociated syndecan-1 regulates
the innate immune response to influenza infection by facilitating
cytoprotective signals through c-Met signaling to limit bronchial epithelial
apoptosis, thereby attenuating lung injury and inflammation.
Keywords: influenza; lung injury; syndecan-1; proteoglycan;
c-Met