V. Besnard et al., Distinct patterns of insulin-like growth factor binding protein (IGFBP)-2 and TGFBP-3 expression in oxidant exposed lung epithelial cells, BBA-MOL CEL, 1538(1), 2001, pp. 47-58
Citations number
37
Categorie Soggetti
Cell & Developmental Biology
Journal title
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
Oxygen (O-2) species are involved in a large variety of pulmonary diseases.
Among the various cell types that compose the lung, the epithelial cells o
f the alveolar structure appear to be a major target for oxidant injury. De
spite their importance in the repair processes, the mechanisms which regula
te the replication of the stem cells of the alveolar epithelium, the type 2
cells, remain poorly understood. Based on the results of several studies w
hich have documented the involvement of the insulin-like growth factor (IGF
) system in lung epithelial cell replication, and which have also suggested
a role for IGF binding proteins (IGFBPs) in the control of cell proliferat
ion, the aim of the present work was to determine whether IGFBPs could be i
nvolved in the modulation of growth of human lung epithelial cells exposed
to oxidants. Experiments were performed using a human lung adenocarcinoma c
ell line (A549) which was exposed for various durations to hyperoxia (95% O
-2). We observed a rapid and reversible growth arrest of the cells after on
ly 24 h of O-2 exposure. When oxidant injury was prolonged, growth arrest w
as followed by induction of apoptosis with activation of the Fas pathway. T
hese effects were associated with an increased expression of IGFBP-2 and IG
FBP-3. In addition, study of localization of these proteins revealed distin
ct patterns of distribution. IGFBP-3 was mainly present in the extracellula
r compartment. In comparison, the fraction of IGFBP-2 secreted was less abu
ndant whereas the IGFBP-2 fraction in the intracellular compartment appeare
d stronger. In addition, analysis of the subcellular localization provided
data indicating the presence of IGFBP-2 in the nucleus. Taken together thes
e data support a role for IGFBP-2. and IGFBP-3 in the processes of growth a
rrest and apoptosis in lung epithelial cells upon oxidant exposure. They al
so suggest that distinct mechanisms may link IGFBP-2 and IGFBP-3 to the key
regulators of the cell cycle. (C) 2001 Elsevier Science B.V. All rights re
served.