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
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.