title: Modulation of IGF-binding protein-2 and -3 in hyperoxic injury in developing rat lung.
abstract: Retinoids play an important role in lung development and repair. We showed that retinoic acid (RA) inhibits O(2)-induced fibroblast proliferation in rat lung explants. IGF-1, which enhances the proliferation of human fetal lung fibroblasts and stimulates collagen production during lung injury, has an important role in the lung injury/repair process. Interactions of IGF-1 with its receptor are modulated by IGF-binding proteins IGFBPs. We hypothesized that RA alters IGFBP-2 and -3 in hyperoxia-exposed neonatal lung and alters collagen production. Neonatal rat lungs were cultured in room air or 95% O(2) and 5% CO(2) for 3 d with or without RA. IGFBP-2 and -3 were measured both in culture medium and in lung tissue. Type I collagen and procollagen propeptide were analyzed in the lung tissue. Hyperoxia induced an increase in type I collagen that was significantly inhibited in the presence of RA. IGFBP-2 and IGFBP-3 in the lungs were decreased in hyperoxia but significantly increased in hyperoxia plus RA. In the culture medium, IGFBP-2 and -3 were not increased with hyperoxia but significantly increased in the presence of RA plus hyperoxia. There was no increase in IGFBP-3 RNA transcript after RA treatment in either room air or O(2) exposure. In conclusion, RA modulates the secreted IGFBP-2 and -3 during O(2) exposure and inhibits the increase in collagen that occurs during lung injury. We speculate that RA protects against O(2)-induced neonatal lung injury through modulation of the IGFBPs.
authors.affiliation: Floating Hospital for Children, New England Medical Center and Tufts Medical School, Boston, Massachusetts 02111, USA. achetty@tufts-nemc.org
authors.forename: Anne
authors.initials: A
authors.lastname: Chetty
authors.forename: Nicholas
authors.initials: N
authors.lastname: Manzo
authors.forename: Aaron B
authors.initials: AB
authors.lastname: Waxman
authors.forename: Heber C
authors.initials: HC
authors.lastname: Nielsen
mesh_terms: D000818:Animals; D015153:Blotting, Western; D049109:Cell Proliferation; D003094:Collagen / Q000378:metabolism; D024042:Collagen Type I / Q000378:metabolism; D003470:Culture Media; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000378:metabolism; D000860:Hypoxia; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000096:biosynthesis*; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000096:biosynthesis*; D008168:Lung / Q000196:embryology* / Q000378:metabolism; D055370:Lung Injury; D010100:Oxygen / Q000378:metabolism; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D012260:Ribonucleases / Q000378:metabolism; D013997:Time Factors; D014212:Tretinoin / Q000378:metabolism; D014945:Wound Healing
chemical_list: D024042:Collagen Type I; D003470:Culture Media; D018971:Insulin-Like Growth Factor Binding Protein 2; D018972:Insulin-Like Growth Factor Binding Protein 3; D012333:RNA, Messenger; D014212:Tretinoin; D012313:RNA; D003094:Collagen; D012260:Ribonucleases; D010100:Oxygen