HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 297/2/L286    most recent 00094.2009v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (1) Google Scholar Articles by Xu, Y. Articles by Ikegami, M. PubMed PubMed Citation Articles by Xu, Y. Articles by Ikegami, M.

C/EBP is required for pulmonary cytoprotection during hyperoxia

Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio

Submitted 20 March 2009 ; accepted in final form 21 May 2009

A number of transcriptional pathways regulating fetal lung development are active during repair of the injured lung. We hypothesized that C/EBP, a transcription factor critical for lung maturation, plays a role in protection of the alveolar epithelium following hyperoxic injury of the mature lung. Transgenic Cebp^/ mice, in which Cebp was conditionally deleted from Clara cells and type II cells after birth, were developed. While no pulmonary abnormalities were observed in the Cebp^/ mice (7–8 wk old) under normal conditions, the mice were highly susceptible to hyperoxia. Cebp^/ mice died within 4 days of exposure to 95% oxygen in association with severe lung inflammation, altered maturation of surfactant protein B and C, decreased surfactant lipid secretion, and abnormal lung mechanics at a time when all control mice survived. mRNA microarray analysis of isolated type II cells at 0, 2, and 24 h of hyperoxia demonstrated the reduced expression of number of genes regulating surfactant lipid and protein homeostasis, including Srebf, Scap, Lpcat1, Abca3, Sftpb, and Napsa. Genes influencing cell signaling or immune responses were induced in the lungs of Cebp^/ mice. C/EBP was required for the regulation of genes associated with surfactant lipid homeostasis, surfactant protein biosynthesis, processing and transport, defense response to stress, and cell redox homeostasis during exposure to hyperoxia. While C/EBP did not play a critical role in postnatal pulmonary function under normal conditions, C/EBP mediated protection of the lung during acute lung injury induced by hyperoxia.

Vnn1; GSH; microarray; Napsa; surfactant

This article has been cited by other articles:

				M.-L. Franco-Montoya, J. R. Bourbon, X. Durrmeyer, S. Lorotte, P.-H. Jarreau, and C. Delacourt Pulmonary effects of keratinocyte growth factor in newborn rats exposed to hyperoxia Am J Physiol Lung Cell Mol Physiol, November 1, 2009; 297(5): L965 - L976. [Abstract] [Full Text] [PDF]