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Publication : CYR61 (CCN1) overexpression induces lung injury in mice.

First Author  Grazioli S Year  2015
Journal  Am J Physiol Lung Cell Mol Physiol Volume  308
Issue  8 Pages  L759-65
PubMed ID  25713320 Mgi Jnum  J:232270
Mgi Id  MGI:5776427 Doi  10.1152/ajplung.00190.2014
Citation  Grazioli S, et al. (2015) CYR61 (CCN1) overexpression induces lung injury in mice. Am J Physiol Lung Cell Mol Physiol 308(8):L759-65
abstractText  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.
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