Open Access Research article

Developmental expression of the receptor for advanced glycation end-products (RAGE) and its response to hyperoxia in the neonatal rat lung

Pierre-Paul Lizotte1, Lana E Hanford2, Jan J Enghild3, Eva Nozik-Grayck4, Brenda-Louise Giles15 and Tim D Oury2*

Author Affiliations

1 Biology of Breathing Research, Manitoba Institute of Child Health, Winnipeg, MB, Canada

2 Department of Pathology, University of Pittsburgh, Pittsburgh, PA, USA

3 Department of Molecular Biology, University of Aarhus, Aarhus C, Denmark

4 Department of Pediatrics, University of Colorado, Denver, CO, USA

5 Department of Pediatrics & Child Health and of Physiology, University of Manitoba, Winnipeg, MB, Canada

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BMC Developmental Biology 2007, 7:15  doi:10.1186/1471-213X-7-15

Published: 7 March 2007

Abstract

Background

The receptor for advanced glycation end products (mRAGE) is associated with pathology in most tissues, while its soluble form (sRAGE) acts as a decoy receptor. The adult lung is unique in that it expresses high amounts of RAGE under normal conditions while other tissues express low amounts normally and up-regulate RAGE during pathologic processes. We sought to determine the regulation of the soluble and membrane isoforms of RAGE in the developing lung, and its expression under hyperoxic conditions in the neonatal lung.

Results

Fetal (E19), term, 4 day, 8 day and adult rat lung protein and mRNA were analyzed, as well as lungs from neonatal (0–24 hrs) 2 day and 8 day hyperoxic (95% O2) exposed animals. mRAGE transcripts in the adult rat lung were 23% greater than in neonatal (0–24 hrs) lungs. On the protein level, rat adult mRAGE expression was 2.2-fold higher relative to neonatal mRAGE expression, and adult sRAGE protein expression was 2-fold higher compared to neonatal sRAGE. Fetal, term, 4 day and 8 day old rats had a steady increase in both membrane and sRAGE protein expression evaluated by Western Blot and immunohistochemistry. Newborn rats exposed to chronic hyperoxia showed significantly decreased total RAGE expression compared to room air controls.

Conclusion

Taken together, these data show that rat pulmonary RAGE expression increases with age beginning from birth, and interestingly, this increase is counteracted under hyperoxic conditions. These results support the emerging concept that RAGE plays a novel and homeostatic role in lung physiology.