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Department of Pediatric Pulmonology, Institut National de la Santé et de la Recherche Médicale U142, Trousseau Hospital, St. Antoine Medical School, University of Paris, 75012 Paris, France
Retinoids, including retinol and retinoic acid
(RA) derivatives, are important molecules for lung growth and
homeostasis. The presence of RA receptors and of RA-binding proteins in
the alveolar epithelium led to suggest a role for RA on alveolar
epithelial cell replication. In the present study, we examined the
effects of RA on proliferation of the stem cells of the alveolar
epithelium, the type 2 cells. We showed that treatment of
serum-deprived type 2 cells with RA led to a stimulation of cell
proliferation, with an increase in cell number in a dose-dependent
manner. To gain some insights into the mechanisms involved, we studied
the effects of RA on the expression of several components of the
insulin-like growth factor (IGF) system that have been shown to be
associated with the growth arrest of type 2 cells, mainly the
IGF-binding protein-2 (IGFBP-2), IGF-II, and the type 2 IGF receptor.
We documented a marked decrease in the expression of these components
upon RA treatment. Using conditioned media from RA-treated cells, we
provided evidence that the proliferative response of type 2 cells to RA was mediated through production of growth factor(s) distinct from IGF-I. We also showed that RA was able to reduce the decrease in cell
number observed when type 2 cells were treated with transforming growth
factor (TGF)-
1. These results together with the known stimulatory
effect of TGF-1 on IGFBP-2 expression led to suggest that RA may be
associated with type 2 cell proliferation through mechanisms
interfering with the TGF-1 pathway.
alveolar epithelial cell; retinoic acid; insulin-like growth
factor; transforming growth factor-
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