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Am J Respir Crit Care Med. 2016 Aug 1;194(3):333-44. doi: 10.1164/rccm.201509-1878OC.

Syndecan-1 Attenuates Lung Injury during Influenza Infection by Potentiating c-Met Signaling to Suppress Epithelial Apoptosis.

Author information

1
1 Women's Guild Lung Institute, Cedars-Sinai Medical Center; Los Angeles, California; and.
2
2 Division of Pulmonary and Critical Care Medicine, Department of Medicine.
3
3 Department of Pathology, and.
4
4 Department of Pediatrics, University of Washington, Seattle, Washington.

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 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.

KEYWORDS:

c-Met; influenza; lung injury; proteoglycan; syndecan-1

PMID:
26959387
PMCID:
PMC4970595
DOI:
10.1164/rccm.201509-1878OC
[Indexed for MEDLINE]
Free PMC Article

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