Retinoic acid and erythropoietin maintain alveolar development in mice treated with an angiogenesis inhibitor

Su Jin Cho, Caroline L.S. George, Jeanne M. Snyder, Michael J. Acarregui

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

Bronchopulmonary dysplasia in premature infants is characterized by inhibited alveolarization and vasculogenesis. Our goal was to generate a mouse model of inhibited alveolarization by the administration of an inhibitor of angiogenesis. We then examined the effects of retinoic acid (RA) and erythropoietin (EPO) on alveolar development in this model. Three-day-old mice were injected with a single dose of SU1498 (30 mg/kg, subcutaneously) and either concomitant RA (2 mg/kg, intraperitoneally) or EPO (2,000 IU/kg, subcutaneously) for 10 consecutive days, then harvested on Day 21. Morphometric and electron microscopic analysis, and platelet endothelial cell adhesion molecule (PECAM) immunostaining of endothelial cells, were performed on the lung tissue. In vitro assays were also performed to characterize the effects of RA on endothelial cell growth. Alveolar development was attenuated in the SU1498-treated mice, and electron microscopy demonstrated dilated and dysmorphic capillaries in alveolar walls comparable to previous findings in lungs of infants with bronchopulmonary dysplasia. RA or EPO maintained mean alveolar volume, alveolar surface area, and endothelial cell volume density in the SU1498-treated animals. RA also increased the proliferation of human fetal lung capillary endothelial precursor cells in vitro. These results suggest that the maintenance or growth of the endothelial cell population of the distal lung plays a major role in postnatal alveolar development.

Original languageEnglish (US)
Pages (from-to)622-628
Number of pages7
JournalAmerican journal of respiratory cell and molecular biology
Volume33
Issue number6
DOIs
StatePublished - Dec 2005

Keywords

  • Alveolar development
  • Angiogenesis inhibition
  • Erythropoietin
  • Retinoic acid
  • SU1498

Fingerprint Dive into the research topics of 'Retinoic acid and erythropoietin maintain alveolar development in mice treated with an angiogenesis inhibitor'. Together they form a unique fingerprint.

Cite this