Migration and gelatinases in cultured fetal, adult, and hyperoxic alveolarepithelial cells

Citation
S. Buckley et al., Migration and gelatinases in cultured fetal, adult, and hyperoxic alveolarepithelial cells, AM J P-LUNG, 281(2), 2001, pp. L427-L434
Citations number
29
Language
INGLESE
art.tipo
Article
Categorie Soggetti
da verificare
Journal title
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
ISSN journal
1040-0605 → ACNP
Volume
281
Issue
2
Year of publication
2001
Pages
L427 - L434
Database
ISI
SICI code
1040-0605(200108)281:2<L427:MAGICF>2.0.ZU;2-U
Abstract
Alveolar epithelial cell (AEC) migration mediated by matrix metalloproteina ses (MMPs) is required for lung development and repair after injury such as hyperoxia. Of specific interest in lung remodeling are the gelatinases, wh ich are upregulated in AEC after hyperoxia. We correlated migration and gel atinase production in AEC cultured from fetal, adult, and hyperoxic rats. F etal 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 AE C migrated and expressed MMP-2 and MMP-9 proteins only after 48 h of cultur e. AEC from hyperoxic rats were significantly more migratory through gelati n than control adult AEC, with significantly higher MMP-9 activity. Inhibit ion of MMPs with doxycycline reduced the migration of AEC from hyperoxic ra ts 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 vit ro, and we speculate that MMPs may play a key mechanistic role in AEC migra tion in vivo during lung development and repair.