Skip Navigation
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

National Institute of Environmental Health Sciences

Use this QR code to view the newest version of this document
Use this QR code to view the newest version of this document

Your Environment. Your Health.

Publication Detail

Title: Opposing regulation of human alveolar type II cell differentiation by nitric oxide and hyperoxia.

Authors: Johnston, Lindsay C; Gonzales, Linda W; Lightfoot, Richard T; Guttentag, Susan H; Ischiropoulos, Harry

Published In Pediatr Res, (2010 May)

Abstract: Clinical trials demonstrated decreasing rates of bronchopulmonary dysplasia in preterm infants with hypoxic respiratory failure treated with inhaled nitric oxide (iNO). However, the molecular and biochemical effects of iNO on developing human fetal lungs remain vastly unknown. By using a well-characterized model of human fetal alveolar type II cells, we assessed the effects of iNO and hyperoxia, independently and concurrently, on NO-cGMP signaling pathway and differentiation. Exposure to iNO increased cGMP levels by 40-fold after 3 d and by 8-fold after 5 d despite constant expression of phosphodiesterase-5 (PDE5). The levels of cGMP declined significantly on exposure to iNO and hyperoxia at 3 and 5 d, although expression of soluble guanylyl cyclase (sGC) was sustained. Surfactant proteins B and C (SP-B, SP-C) and thyroid transcription factor (TTF)-1 mRNA levels increased in cells exposed to iNO in normoxia but not on exposure to iNO plus hyperoxia. Collectively, these data indicate an increase in type II cell markers when undifferentiated lung epithelial cells are exposed to iNO in room air. However, hyperoxia overrides these potentially beneficial effects of iNO despite sustained expression of sGC.

PubMed ID: 20098340 Exiting the NIEHS site

MeSH Terms: Alveolar Epithelial Cells/metabolism*; Biomarkers/metabolism; Cell Differentiation*; Cell Hypoxia; Cells, Cultured; Cyclic GMP/metabolism; Cyclic Nucleotide Phosphodiesterases, Type 5/metabolism; Gene Expression Regulation; Gestational Age; Guanylate Cyclase/metabolism; Humans; Nitric Oxide/metabolism*; Nuclear Proteins/genetics; Oxygen/metabolism*; Pulmonary Surfactant-Associated Protein B/genetics; Pulmonary Surfactant-Associated Protein C/genetics; RNA, Messenger/metabolism; Receptors, Cytoplasmic and Nuclear/metabolism; Signal Transduction; Soluble Guanylyl Cyclase; Thyroid Nuclear Factor 1; Time Factors; Transcription Factors/genetics

Back
to Top