Kuang Ping-Ping, Goldstein Ronald H, Liu Yue, Rishikof David C, Jean Jyh-Chang, Joyce-Brady Martin
The Pulmonary Center, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
Am J Physiol Lung Cell Mol Physiol. 2003 Nov;285(5):L1147-52. doi: 10.1152/ajplung.00098.2003. Epub 2003 Aug 8.
Fibulin-5, previously known as DANCE and EVEC, is a secreted extracellular matrix protein that functions as a scaffold for elastin fiber assembly and as a ligand for integrins alphavbeta3, alphavbeta5, and alpha9beta1. Fibulin-5 is developmentally regulated in the lung, and lung air space enlargement develops in mice deficient in fibulin-5. Fibulin-5 is also induced in adult lung following lung injury by hyperoxia. To further examine the role of fibulin-5 during repair of lung injury, we assessed fibulin-5 expression during elastase-induced emphysema in C57/b mice. Mice were treated with either saline or elastase via the trachea, and the lung was examined 20 days after treatment. Fibulin-5 mRNA was induced almost fourfold, whereas elastin mRNA was minimally elevated. Immunohistochemistry studies showed that fibulin-5 was induced in cells within the alveolar wall following elastase treatment. Western analysis demonstrates that fibulin-5 was strongly expressed in isolated primary lung interstitial fibroblasts. Fibulin-5 protein was localized to the fibroblast cell layer in culture, and brief elastase treatment degraded the protein. Intact fibulin-5 did not accumulate in the culture media. Treatment of fibroblasts with the proinflammatory cytokine interleukin-1beta abolished fibulin-5 mRNA expression. Our results indicate that fibulin-5 is coordinately expressed and regulated with elastin in lung fibroblasts and may serve a key role during lung injury and repair.
纤维连接蛋白5，以前称为DANCE和EVEC，是一种分泌型细胞外基质蛋白，它作为弹性纤维组装的支架以及整合素αvβ3、αvβ5和α9β1的配体发挥作用。纤维连接蛋白5在肺中受到发育调控，在缺乏纤维连接蛋白5的小鼠中会出现肺气腔扩大。在高氧导致的成年肺损伤后，纤维连接蛋白5也会被诱导表达。为了进一步研究纤维连接蛋白5在肺损伤修复过程中的作用，我们评估了C57/b小鼠在弹性蛋白酶诱导的肺气肿过程中纤维连接蛋白5的表达情况。通过气管给小鼠注射生理盐水或弹性蛋白酶进行处理，在处理后20天检查肺组织。纤维连接蛋白5 mRNA的表达几乎增加了四倍，而弹性蛋白mRNA的升高幅度很小。免疫组织化学研究表明，弹性蛋白酶处理后，肺泡壁内的细胞中诱导表达了纤维连接蛋白5。蛋白质印迹分析表明，纤维连接蛋白5在分离的原代肺间质成纤维细胞中强烈表达。纤维连接蛋白5蛋白定位于培养的成纤维细胞层，短暂的弹性蛋白酶处理会使该蛋白降解。完整的纤维连接蛋白5不会在培养基中积累。用促炎细胞因子白细胞介素-1β处理成纤维细胞可消除纤维连接蛋白5 mRNA的表达。我们的结果表明，纤维连接蛋白5在肺成纤维细胞中与弹性蛋白协同表达和调控，可能在肺损伤和修复过程中起关键作用。
