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

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.

• Authors: Rena Brauer, Lingyin Ge, Saundra Y Schlesinger, Timothy P Birkland, Ying Huang, Tanyalak Parimon, Vivian Lee, Bonnie L McKinney, John K McGuire, William C Parks, Peter Chen
• Journal: American journal of respiratory and critical care medicine (Am J Respir Crit Care Med) Vol. 194 Issue 3 Pg. 333-44 (08 01 2016) ISSN: 1535-4970 [Electronic] United States
• PMID: 26959387 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural)

Chemical References

• Syndecan-1
• Proto-Oncogene Proteins c-met

Topics

• Animals
• Apoptosis (immunology)
• Disease Models, Animal
• Epithelial Cells (immunology)
• Humans
• Immunity, Innate (immunology)
• Influenza A Virus, H1N1 Subtype (immunology)
• Lung (immunology)
• Lung Injury (immunology, prevention & control)
• Mice
• Orthomyxoviridae Infections (immunology)
• Proto-Oncogene Proteins c-met (genetics, immunology)
• Signal Transduction (immunology)
• Syndecan-1 (immunology, pharmacology)