Organ culture as a model of alveolar development

M. J. Kresch, C. Christian, L. Zhu, N. Hussain

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Abstract

Explants of fetal rat lung have been a useful model to study fetal rat lung development. The alveolar phase of rat lung development begins just prior to birth and continues for the first 3 weeks of life. The cellular and molecular mechanisms of alveolar formation have not been studied. We have previously shown that there is an abrupt increase in apoptosis of lung mesenchyme around the time of birth in rat lung. We formulated the hypothesis that the regulated balance between apoptosis and cell proliferation is a key mechanism by which the lung remodels during the alveolar phase of lung development. The goal of this study was to determine the usefulness of the organ culture model for the study of early alveolar lung development. Explants of 21 days' gestation (term=22 days) fetal rat lung were placed in explant culture for 0-7 days. At each day tissue was harvested for protein extraction, total RNA extraction and histologic analysis. Immunoblots using appropriate primary antibodies were used to measure changes in SP-A receptor (specific marker of type II cells) and p21 (marker of cell cycle arrest). Northern blots measured changes in steady state levels of mRNA for α-1 procollagen (marker of alveolar septal formation). Apoptosis was quantified using the TUNEL assay in histologic sections. We found increased apoptosis in explants after 0-2 days in culture corresponding to the increased levels of apoptosis measured in vivo. These changes in culture occurred concomitantly with increased levels of p21. We also found increased levels of SP-A receptor after 1-2 days in culture. Levels of α-1 procollagen mRNA increased after 5 days in culture. We conclude that the explant culture is a useful model for study of the early events during the alveolar phase of lung development: 1) increased apoptosis and cell cycle arrest; 2) increased alveolar septum formation; 3) increased specific markers of type II cells.

Original languageEnglish (US)
Pages (from-to)166A
JournalJournal of Investigative Medicine
Volume47
Issue number2
StatePublished - Feb 1999

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

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    Kresch, M. J., Christian, C., Zhu, L., & Hussain, N. (1999). Organ culture as a model of alveolar development. Journal of Investigative Medicine, 47(2), 166A.