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首页> 外文期刊>American Journal of Physiology >Migration and gelatinases in cultured fetal, adult, and hyperoxic alveolar epithelial cells.
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Migration and gelatinases in cultured fetal, adult, and hyperoxic alveolar epithelial cells.

机译：培养的胎儿，成年和高氧肺泡上皮细胞中的迁移和明胶酶。

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摘要

Alveolar epithelial cell (AEC) migration mediated by matrix metalloproteinases (MMPs) is required for lung development and repair after injury such as hyperoxia. Of specific interest in lung remodeling are the gelatinases, which are upregulated in AEC after hyperoxia. We correlated migration and gelatinase production in AEC cultured from fetal, adult, and hyperoxic rats. Fetal AEC (19-20 days) had higher MMP-2 and MMP-9 gelatinase expression than adult AEC, with fivefold higher MMP-9 activity, and were migratory through gelatin, responding to epidermal growth factor, keratinocyte growth factor, and fibroblast growth factor-10. MMP-2 and MMP-9 expression and migratory activity could be detected from the time of plating. In contrast, adult AEC migrated and expressed MMP-2 and MMP-9 proteins only after 48 h of culture. AEC from hyperoxic rats were significantly more migratory through gelatin than control adult AEC, with significantly higher MMP-9 activity. Inhibition of MMPs with doxycycline reduced the migration of AEC from hyperoxic rats to the level of control adult AEC. Fibronectin-cultured "hyperoxic" AEC acquired a temporary capacity for migration similar to the A549 lung cancer cell line, which is both highly migratory and invasive and is derived from the AEC type 2 lineage. These data suggest that MMP activity is associated with a migratory phenotype in fetal, hyperoxic, and transformed AEC in vitro, and we speculate that MMPs may play a key mechanistic role in AEC migration in vivo during lung development and repair.
机译：由基质金属蛋白酶（MMP）介导的肺泡上皮细胞（AEC）迁移是肺损伤和高氧等损伤后肺发育和修复所必需的。明胶酶是肺重塑中特别感兴趣的物质，高氧后在AEC中上调。我们关联了从胎儿，成年和高氧大鼠培养的AEC中的迁移和明胶酶的产生。胎儿AEC（19-20天）的MMP-2和MMP-9明胶酶表达高于成人AEC，MMP-9活性高五倍，并且可以通过明胶迁移，对表皮生长因子，角质形成细胞生长因子和成纤维细胞生长有反应因子10。从接种开始就可以检测出MMP-2和MMP-9的表达以及迁移活性。相反，成年AEC仅在培养48小时后才迁移并表达MMP-2和MMP-9蛋白。高氧大鼠的AEC通过明胶的迁移明显高于对照组成年AEC，其MMP-9活性更高。强力霉素对MMP的抑制作用可降低AEC从高氧大鼠的迁移至对照组成年AEC的水平。纤连蛋白培养的“高氧” AEC具有与A549肺癌细胞系相似的临时迁移能力，该细胞系高度迁移且具有侵袭性，并源自AEC 2型谱系。这些数据表明，MMP活性与胎儿，高氧和体外转化的AEC中的迁移表型有关，我们推测MMP在肺发育和修复过程中可能在体内AEC迁移中发挥关键的机械作用。

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