Background:Receptors for advanced glycation end products (RAGE) have been implicated in fibrotic processes. We hypothesized that lung fibrosis induced by maternal lipopolysaccharide (LPS)-mediated inflammation and neonatal hyperoxia involves RAGE in newborn rats.Methods:Pregnant Sprague-Dawley rats received intraperitoneal injections of LPS or normal saline (NS) on 20 and 21 d of gestation. The pups were reared in room air (RA) or an O 2-enrich atmosphere (O 2), creating the four study groups, NS + RA, NS + O 2, LPS + RA, and LPS + O 2. The O 2 treatment was >95% O 2 for 7 d, followed by 60% O 2 for 14 d.Results:Rat pups born to LPS-injected dams exhibited significantly higher lung interferon-γ and interleukin-1β (IL-1β) on postnatal day 7 than the pups born to NS-injected dams. Rat pups reared in hyperoxia expressed higher lung IL-10 on postnatal day 7, compared with the RA-reared pups. The LPS + O 2 group had significantly higher total collagen and transforming growth factor-β1 on postnatal days 7 and 21 than the NS+RA group. RAGE mRNA and sRAGE protein expression were significantly lower in the LPS + O 2 group on postnatal day 7 than the NS+RA group.Conclusion:RAGE may be involved in the pathogenesis of lung fibrosis induced by maternal systemic inflammation and postnatal hyperoxia in rat neonates.
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