Syndecan-1 attenuates lung injury during influenza infection by potentiating c-Met signaling to suppress epithelial apoptosis

R Brauer, L Ge, SY Schlesinger… - American Journal of …, 2016 - atsjournals.org
R Brauer, L Ge, SY Schlesinger, TP Birkland, Y Huang, T Parimon, V Lee, BL McKinney…
American Journal of Respiratory and Critical Care Medicine, 2016atsjournals.org
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 Sdc1−/− mice were infected with a H1N1 virus (PR8)
as an experimental model of influenza infection. Human and murine airway epithelial cell …
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 Sdc1−/− 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 and lung injury in Sdc1−/− mice compared with WT mice 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. Our findings demonstrate a novel mechanism in which cell membrane–associated 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.
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