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Mouse Embryonic Lung Culture, A System to Evaluate the Molecular Mechanisms of Branching
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Adrenomedullin expression in the developing human fetal lung.

Carlos G Ramos1, Xi Sun, Eric B Johnson

  • 1From the *Division of Neonatology, Department of Pediatrics, School of Medicine, University of New Mexico; †Biostatistics Core, School of Medicine, University of New Mexico; ‡Department of Cell Biology and Physiology, School of Medicine, University of New Mexico, Albuquerque, NM.

Journal of Investigative Medicine : the Official Publication of the American Federation for Clinical Research
|October 31, 2013
PubMed
Summary

Adrenomedullin (AM) is present in developing human lungs. Its expression and that of its AM1 receptor components increase with gestational age, suggesting a key role in lung development.

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Area of Science:

  • Pulmonary Medicine
  • Developmental Biology
  • Endocrinology

Background:

  • Adrenomedullin (AM) is a bioactive peptide with known roles in cardiovascular and respiratory health.
  • Its specific function in human fetal lung development, including vascular and alveolar growth, remains largely uncharacterized.

Purpose of the Study:

  • To investigate the expression patterns of Adrenomedullin (AM) and its receptor components, calcitonin-receptor-like receptor (CRLR), receptor activity-modifying protein (RAMP)2, and RAMP3, in the developing human fetal lung.
  • To determine if AM expression changes with advancing gestational age (10–24 weeks).

Main Methods:

  • Quantitative analysis of messenger RNA (mRNA) for AM, CRLR, RAMP2, and RAMP3 using real-time reverse-transcription polymerase chain reaction (RT-PCR).
  • Assessment of Adrenomedullin protein levels via Western blot analysis.
  • Immunohistochemical localization of AM and its receptor components within fetal lung tissue sections.

Main Results:

  • Transcripts for AM, CRLR, RAMP2, and RAMP3 were detected in midgestation human fetal lungs.
  • Gene expression of AM, CRLR, and RAMP2 significantly increased with advancing gestational age.
  • Conversely, RAMP3 gene expression decreased as gestation progressed, and Adrenomedullin protein levels also showed an increase.

Conclusions:

  • Adrenomedullin is expressed in the midgestation human fetal lung, with increasing gene and protein expression correlating with gestational age.
  • The observed upregulation of AM, CRLR, and RAMP2 suggests a crucial role for the AM1 receptor pathway in human lung development.
  • The differential expression of RAMP3 indicates distinct roles for AM2 receptors, warranting further investigation into their specific functions in fetal lung development.