Matrix Metalloproteinase-7 Coordinates Airway Epithelial Injury Response and Differentiation of Ciliated Cells
Matrix Metalloproteinase-7 Coordinates Airway Epithelial Injury Response and Differentiation of Ciliated Cells
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DOI：
10.1165/rcmb.2012-0083oc
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发表时间：
2013-03-01
影响因子：
6.4
通讯作者：
Chen, Peter
中科院分区：
文献类型：
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作者：
Gharib, Sina A.;Altemeier, William A.;Chen, Peter
基质金属蛋白酶-7（MMP-7）在损伤后表达迅速上调，并发挥调节创伤修复和各种粘膜免疫过程的作用。我们评估了在气液界面培养的野生型和Mmp 7缺失小鼠气道上皮细胞的整体转录反应。损伤后基因型之间差异表达基因的分析显示与炎症，纤毛和分化相关的功能类别的丰富。因为这些分析表明，MMP 7调节纤毛细胞的形成，我们评估了恢复野生型和MMP 7基因敲除小鼠体内萘损伤后，这表明增强纤毛细胞的形成，在没有MMP 7。此外，在空气-液体界面培养中评估细胞分化的体外研究也显示，与野生型条件相比，在Mmp 7无效条件下纤毛细胞的产生更快。这些研究确定了MMP 7在伤口修复过程中减弱纤毛细胞分化的新作用。
Matrix metalloproteinase-7 (MMP7) expression is quickly up-regulated after injury, and functions to regulate wound repair and various mucosal immune processes. We evaluated the global transcriptional response of airway epithelial cells from wild-type and Mmp7-null mice cultured at an air-liquid interface. The analysis of differentially expressed genes between genotypes after injury revealed an enrichment of functional categories associated with inflammation, cilia, and differentiation. Because these analyses suggested that MMP7 regulated ciliated cell formation, we evaluated the recovery of the airway epithelium in wild-type and Mmp7-null mice in vivo after naphthalene injury, which revealed augmented ciliated cell formation in the absence of MMP7. Moreover, in vitro studies evaluating cell differentiation in air-liquid interface cultures also showed faster ciliated cell production under Mmp7-null conditions compared with wild-type conditions. These studies identified a new role for MMP7 in attenuating ciliated cell differentiation during wound repair.