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

Lizotte PP, Hanford LE, Enghild JJ, Nozik-Grayck E, Giles BL, Oury TD - BMC Dev. Biol. (2007)

Bottom Line: 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.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.These results support the emerging concept that RAGE plays a novel and homeostatic role in lung physiology.

View Article: PubMed Central - HTML - PubMed

Affiliation: Biology of Breathing Research, Manitoba Institute of Child Health, Winnipeg, MB, Canada. pierre_paul_00@yahoo.com <pierre_paul_00@yahoo.com>

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.

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RAGE mRNA quantified by real-time RT-PCR. Rat lung RAGE mRNA was quantified by real time PCR amplification. These studies show an increase in adult RAGE mRNA compared to neonates. Results are expressed as inversed crossing-thresholds (CT) normalized to β-actin n = 3 (*p < 0.05).
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Figure 2: RAGE mRNA quantified by real-time RT-PCR. Rat lung RAGE mRNA was quantified by real time PCR amplification. These studies show an increase in adult RAGE mRNA compared to neonates. Results are expressed as inversed crossing-thresholds (CT) normalized to β-actin n = 3 (*p < 0.05).

Mentions: To examine the developmental expression of RAGE and its isoforms in the lung, mRAGE and sRAGE protein levels were analyzed in rat neonatal (0–24 h) and adult lungs. Western blot analysis revealed a 2-fold increase of mRAGE expression in the adult lung compared to that seen in the neonate (Fig. 1A). Western blot analysis of sRAGE revealed a similar trend in which sRAGE expression was significantly increased in the adult lung compared to the neonatal lung (Fig. 1B). A representative Western blot reveals a molecular weight variance between neonatal sRAGE compared to adult sRAGE (Fig. 1C). This difference in size is likely due to a difference in glycosylation (see below). Real-time RT-PCR amplification revealed a 23% increase in adult mRAGE mRNA compared to neonatal mRNA levels (Fig. 2) (p < 0.05).


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

Lizotte PP, Hanford LE, Enghild JJ, Nozik-Grayck E, Giles BL, Oury TD - BMC Dev. Biol. (2007)

RAGE mRNA quantified by real-time RT-PCR. Rat lung RAGE mRNA was quantified by real time PCR amplification. These studies show an increase in adult RAGE mRNA compared to neonates. Results are expressed as inversed crossing-thresholds (CT) normalized to β-actin n = 3 (*p < 0.05).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC1828052&req=5

Figure 2: RAGE mRNA quantified by real-time RT-PCR. Rat lung RAGE mRNA was quantified by real time PCR amplification. These studies show an increase in adult RAGE mRNA compared to neonates. Results are expressed as inversed crossing-thresholds (CT) normalized to β-actin n = 3 (*p < 0.05).
Mentions: To examine the developmental expression of RAGE and its isoforms in the lung, mRAGE and sRAGE protein levels were analyzed in rat neonatal (0–24 h) and adult lungs. Western blot analysis revealed a 2-fold increase of mRAGE expression in the adult lung compared to that seen in the neonate (Fig. 1A). Western blot analysis of sRAGE revealed a similar trend in which sRAGE expression was significantly increased in the adult lung compared to the neonatal lung (Fig. 1B). A representative Western blot reveals a molecular weight variance between neonatal sRAGE compared to adult sRAGE (Fig. 1C). This difference in size is likely due to a difference in glycosylation (see below). Real-time RT-PCR amplification revealed a 23% increase in adult mRAGE mRNA compared to neonatal mRNA levels (Fig. 2) (p < 0.05).

Bottom Line: 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.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.These results support the emerging concept that RAGE plays a novel and homeostatic role in lung physiology.

View Article: PubMed Central - HTML - PubMed

Affiliation: Biology of Breathing Research, Manitoba Institute of Child Health, Winnipeg, MB, Canada. pierre_paul_00@yahoo.com <pierre_paul_00@yahoo.com>

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.

Show MeSH
Related in: MedlinePlus