title: CYR61 (CCN1) overexpression induces lung injury in mice.
abstract: Cysteine-rich protein-61 (CYR61), also known as connective tissue growth factor, CYR61, and nephroblastoma overexpressed gene 1 (CCN1), is a heparin-binding protein member of the CCN family of matricellular proteins. Gene expression profiles showed that Cyr61 is upregulated in human acute lung injury (ALI), but its functional role is unclear. We hypothesized that CYR61 contributes to ALI in mice. First, we demonstrated that CYR61 expression increases after bleomycin-induced lung injury. We then used adenovirus-mediated gene transfer to determine whether CYR61 overexpression in the lungs was sufficient to cause ALI. Mice instilled with CYR61 adenovirus showed greater weight loss, increased bronchoalveolar lavage total neutrophil counts, increased protein concentrations, and increased mortality compared with mice instilled with empty-vector adenovirus. Immunohistochemical studies in lungs from humans with idiopathic pulmonary fibrosis revealed CYR61 expression on the luminal membrane of alveolar epithelial cells in areas of injury. We conclude that CYR61 is upregulated in ALI and that CYR61 overexpression exacerbates ALI in mice.
authors.affiliation: Pediatric Critical Care Unit, University Hospital of Geneva, Geneva, Switzerland; Center for Lung Biology, Division of Pulmonary and Critical Medicine, Department of Medicine, University of Washington, Seattle, Washington;
authors.forename: Serge
authors.initials: S
authors.lastname: Grazioli
authors.affiliation: Center for Lung Biology, Division of Pulmonary and Critical Medicine, Department of Medicine, University of Washington, Seattle, Washington;
authors.forename: Sucheol
authors.initials: S
authors.lastname: Gil
authors.affiliation: Center for Lung Biology, Division of Pulmonary and Critical Medicine, Department of Medicine, University of Washington, Seattle, Washington;
authors.forename: Dowon
authors.initials: D
authors.lastname: An
authors.affiliation: Center for Lung Biology, Division of Pulmonary and Critical Medicine, Department of Medicine, University of Washington, Seattle, Washington;
authors.forename: Osamu
authors.initials: O
authors.lastname: Kajikawa
authors.affiliation: Center for Lung Biology, Division of Pulmonary and Critical Medicine, Department of Medicine, University of Washington, Seattle, Washington;
authors.forename: Alex W
authors.initials: AW
authors.lastname: Farnand
authors.affiliation: Center for Lung Biology, Division of Pulmonary and Critical Medicine, Department of Medicine, University of Washington, Seattle, Washington;
authors.forename: Josiah F
authors.initials: JF
authors.lastname: Hanson
authors.affiliation: Center for Lung Biology, Division of Pulmonary and Critical Medicine, Department of Medicine, University of Washington, Seattle, Washington;
authors.forename: Timothy
authors.initials: T
authors.lastname: Birkland
authors.affiliation: Center for Lung Biology, Division of Pulmonary and Critical Medicine, Department of Medicine, University of Washington, Seattle, Washington;
authors.forename: Peter
authors.initials: P
authors.lastname: Chen
authors.affiliation: Division of Nephrology, Department of Medicine, University of Washington, Seattle, Washington;
authors.forename: Jeremy
authors.initials: J
authors.lastname: Duffield
authors.affiliation: Center for Lung Biology, Division of Pulmonary and Critical Medicine, Department of Medicine, University of Washington, Seattle, Washington;
authors.forename: Lynn M
authors.initials: LM
authors.lastname: Schnapp
authors.affiliation: Center for Lung Biology, Division of Pulmonary and Critical Medicine, Department of Medicine, University of Washington, Seattle, Washington;
authors.forename: William A
authors.initials: WA
authors.lastname: Altemeier
authors.affiliation: Center for Lung Biology, Division of Pulmonary and Critical Medicine, Department of Medicine, University of Washington, Seattle, Washington; Veterans Affairs Puget Sound Healthcare System, Seattle, Washington.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Matute-Bello
mesh_terms: D055371:Acute Lung Injury / Q000378:metabolism*; D000818:Animals; D055515:Cysteine-Rich Protein 61 / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D008168:Lung / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D012128:Respiratory Distress Syndrome / Q000378:metabolism
chemical_list: C491850:CCN1 protein, mouse; D055515:Cysteine-Rich Protein 61
keywords: CCN1; Cysteine-rich protein-61; acute lung injury