CYR61 (CCN1) overexpression induces lung injury in mice
CYR61 (CCN1) overexpression induces lung injury in mice
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DOI：
10.1152/ajplung.00190.2014
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发表时间：
2015-04-15
影响因子：
4.9
通讯作者：
Matute-Bello, Gustavo
中科院分区：
文献类型：
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作者：
Grazioli, Serge;Gil, Sucheol;Matute-Bello, Gustavo
富含半胱氨酸蛋白-61（CYR 61），也称为结缔组织生长因子、CYR 61和肾母细胞瘤过表达基因1（CCN 1），是基质细胞蛋白的CCN家族的肝素结合蛋白成员。基因表达谱显示Cyr 61在人急性肺损伤（ALI）中上调，但其功能作用尚不清楚。我们假设CYR 61参与了小鼠的ALI。首先，我们证明了博来霉素诱导的肺损伤后CYR 61表达增加。然后，我们使用腺病毒介导的基因转移，以确定是否CYR 61在肺过度表达足以导致ALI。与灌注空载体腺病毒的小鼠相比，灌注CYR 61腺病毒的小鼠表现出更大的体重减轻，支气管肺泡灌洗液总中性粒细胞计数增加，蛋白浓度增加和死亡率增加。免疫组织化学研究显示CYR 61在特发性肺纤维化患者肺损伤区肺泡上皮细胞的腔膜上表达。我们的结论是CYR 61在ALI中上调，CYR 61过表达加重了小鼠的ALI。
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.