Neonatal hyperoxia stimulates the expansion of alveolar epithelial type II cells.

Abstract

Supplemental oxygen used to treat infants born prematurely disrupts angiogenesis and is a risk factor for persistent pulmonary disease later in life. Although it is unclear how neonatal oxygen affects development of the respiratory epithelium, alveolar simplification and depletion of type II cells has been observed in adult mice exposed to hyperoxia between postnatal Days 0 and 4. Because hyperoxia inhibits cell proliferation, we hypothesized that it depleted the adult lung of type II cells by inhibiting their proliferation at birth. Newborn mice were exposed to room air (RA) or hyperoxia, and the oxygen-exposed mice were recovered in RA. Hyperoxia stimulated mRNA expressed by type II (Sftpc, Abca3) and type I (T1α, Aquaporin 5) cells and inhibited Pecam expressed by endothelial cells. 5-Bromo-2'-deoxyuridine labeling and fate mapping with enhanced green fluorescence protein controlled statically by the Sftpc promoter or conditionally by the Scgb1a1 promoter revealed increased Sftpc and Abca3 mRNA seen on Day 4 reflected an increase in expansion of type II cells shortly after birth. When mice were returned to RA, this expanded population of type II cells was slowly depleted until few were detected by 8 weeks. These findings reveal that hyperoxia stimulates alveolar epithelial cell expansion when it disrupts angiogenesis. The loss of type II cells during recovery in RA may contribute to persistent pulmonary diseases such as those reported in children born preterm who were exposed to supplemental oxygen.

• Authors: Min Yee, Bradley W Buczynski, Michael A O'Reilly
• Journal: American journal of respiratory cell and molecular biology (Am J Respir Cell Mol Biol) Vol. 50 Issue 4 Pg. 757-66 (Apr 2014) ISSN: 1535-4989 [Electronic] United States
• PMID: 24188066 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Luminescent Proteins
• Pulmonary Surfactant-Associated Protein C
• RNA, Messenger
• SFTPC protein, human
• Scgb1a1 protein, rat
• enhanced green fluorescent protein
• Green Fluorescent Proteins
• Uteroglobin

Topics

• Alveolar Epithelial Cells (metabolism, pathology)
• Animals
• Animals, Newborn
• Cell Proliferation
• Disease Models, Animal
• Gene Expression Regulation
• Genes, Reporter
• Green Fluorescent Proteins (biosynthesis, genetics)
• Hyperoxia (genetics, metabolism, pathology)
• Luminescent Proteins (biosynthesis, genetics)
• Mice
• Mice, Transgenic
• Promoter Regions, Genetic
• Pulmonary Alveoli (metabolism, pathology)
• Pulmonary Surfactant-Associated Protein C (genetics)
• RNA, Messenger (metabolism)
• Time Factors
• Uteroglobin (genetics)
• Red Fluorescent Protein