Coordinate expression of fibulin-5/DANCE and elastin during lung injury repair
Coordinate expression of fibulin-5/DANCE and elastin during lung injury repair
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DOI：
10.1152/ajplung.00098.2003
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发表时间：
2003-11-01
影响因子：
4.9
通讯作者：
Joyce-Brady, M
中科院分区：
文献类型：
--
作者：
Kuang, PP;Goldstein, RH;Joyce-Brady, M
Fibulin-5，以前被称为DANCE和EVEC，是一种分泌的细胞外基质蛋白，作为弹性蛋白纤维组装的支架和整合素α (v) β (3), α (v) β(5)和α (9) β(1)的配体。纤维蛋白-5在肺中受发育调节，缺乏纤维蛋白-5的小鼠肺空间增大。高氧肺损伤后，成人肺中也会产生Fibulin-5。为了进一步研究纤维蛋白-5在肺损伤修复中的作用，我们评估了弹性酶诱导的C57/b小鼠肺气肿中纤维蛋白-5的表达。小鼠分别经气管注射生理盐水或弹性蛋白酶，治疗20天后检查肺组织。Fibulin-5 mRNA几乎被诱导了四倍，而弹性蛋白mRNA则被诱导了最低限度的升高。免疫组织化学研究表明，弹性蛋白酶处理后，肺泡壁内的细胞诱导了纤维蛋白-5。Western分析表明，纤维蛋白-5在分离的原代肺间质成纤维细胞中强烈表达。在培养过程中，纤维蛋白-5蛋白定位于成纤维细胞层，短暂弹性蛋白酶处理可降解该蛋白。完整的纤维蛋白-5未在培养基中积累。用促炎细胞因子白细胞介素-1 β治疗成纤维细胞可消除纤维蛋白-5 mRNA的表达。我们的研究结果表明，纤维蛋白-5在肺成纤维细胞中与弹性蛋白协调表达和调节，可能在肺损伤和修复过程中起关键作用。
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 alpha(v)beta(3), alpha(v)beta(5), and alpha(9)beta(1). 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.