title: Syndecan-1 Attenuates Lung Injury during Influenza Infection by Potentiating c-Met Signaling to Suppress Epithelial Apoptosis.
abstract: 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.
  
  
  
  To determine the mechanism by which syndecan-1 regulates the lung mucosal response to influenza infection.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: 1 Women's Guild Lung Institute, Cedars-Sinai Medical Center; Los Angeles, California; and.|2 Division of Pulmonary and Critical Care Medicine, Department of Medicine.
authors.forename: Rena
authors.identifier: 0000-0002-5900-4853
authors.initials: R
authors.lastname: Brauer
authors.affiliation: 1 Women's Guild Lung Institute, Cedars-Sinai Medical Center; Los Angeles, California; and.
authors.forename: Lingyin
authors.identifier: 0000-0003-0361-9856
authors.initials: L
authors.lastname: Ge
authors.affiliation: 2 Division of Pulmonary and Critical Care Medicine, Department of Medicine.
authors.forename: Saundra Y
authors.initials: SY
authors.lastname: Schlesinger
authors.affiliation: 1 Women's Guild Lung Institute, Cedars-Sinai Medical Center; Los Angeles, California; and.|2 Division of Pulmonary and Critical Care Medicine, Department of Medicine.
authors.forename: Timothy P
authors.initials: TP
authors.lastname: Birkland
authors.affiliation: 1 Women's Guild Lung Institute, Cedars-Sinai Medical Center; Los Angeles, California; and.
authors.forename: Ying
authors.initials: Y
authors.lastname: Huang
authors.affiliation: 1 Women's Guild Lung Institute, Cedars-Sinai Medical Center; Los Angeles, California; and.
authors.forename: Tanyalak
authors.identifier: 0000-0002-4790-0730
authors.initials: T
authors.lastname: Parimon
authors.affiliation: 2 Division of Pulmonary and Critical Care Medicine, Department of Medicine.
authors.forename: Vivian
authors.identifier: 0000-0003-0578-7781
authors.initials: V
authors.lastname: Lee
authors.affiliation: 3 Department of Pathology, and.
authors.forename: Bonnie L
authors.initials: BL
authors.lastname: McKinney
authors.affiliation: 4 Department of Pediatrics, University of Washington, Seattle, Washington.
authors.forename: John K
authors.identifier: 0000-0001-6106-8349
authors.initials: JK
authors.lastname: McGuire
authors.affiliation: 1 Women's Guild Lung Institute, Cedars-Sinai Medical Center; Los Angeles, California; and.|2 Division of Pulmonary and Critical Care Medicine, Department of Medicine.
authors.forename: William C
authors.initials: WC
authors.lastname: Parks
authors.affiliation: 1 Women's Guild Lung Institute, Cedars-Sinai Medical Center; Los Angeles, California; and.|2 Division of Pulmonary and Critical Care Medicine, Department of Medicine.
authors.forename: Peter
authors.identifier: 0000-0002-5330-1718
authors.initials: P
authors.lastname: Chen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D008168:Lung / Q000276:immunology; D055370:Lung Injury / Q000276:immunology / Q000517:prevention & control*; D051379:Mice; D009976:Orthomyxoviridae Infections / Q000276:immunology*; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*; D053668:Syndecan-1 / Q000276:immunology / Q000494:pharmacology*
chemical_list: D053668:Syndecan-1; D019859:Proto-Oncogene Proteins c-met
keywords: c-Met; influenza; lung injury; proteoglycan; syndecan-1