Faculty Collaboration Database

Surfactant-associated protein B is critical to survival in nickel-induced injury in mice. Am J Respir Cell Mol Biol 2009 Aug;41(2):226-36

Date

01/10/2009

Pubmed ID

19131640

Pubmed Central ID

PMC2715910

DOI

10.1165/rcmb.2008-0317OC

Scopus ID

2-s2.0-67651148102 (requires institutional sign-in at Scopus site)   17 Citations

Abstract

The etiology of acute lung injury is complex and associated with numerous, chemically diverse precipitating factors. During acute lung injury in mice, one key event is epithelial cell injury that leads to reduced surfactant biosynthesis. We have previously reported that transgenic mice that express transforming growth factor alpha (TGFA) in the lung were protected during nickel-induced lung injury. Here, we find that the mechanism by which TGFA imparts protection includes maintenance of surfactant-associated protein B (SFTPB) transcript levels and epidermal growth factor receptor-dependent signaling in distal pulmonary epithelial cells. This protection is complex and not accompanied by a diminution in inflammatory mediator transcripts or additional stimulation of antioxidant transcripts. In mouse lung epithelial (MLE-15) cells, microarray analysis demonstrated that nickel increased transcripts of genes enriched in MTF1, E2F-1, and AP-2 transcription factor-binding sites and decreased transcripts of genes enriched in AP-1-binding sites. Nickel also increased Jun transcript and DNA-binding activity, but decreased SFTPB transcript. Expression of SFTPB under the control of a doxycycline-sensitive promoter increased survival during nickel-induced injury as compared with control mice. Together, these findings support the idea that maintenance of SFTPB expression is critical to survival during acute lung injury.

Author List

Bein K, Wesselkamper SC, Liu X, Dietsch M, Majumder N, Concel VJ, Medvedovic M, Sartor MA, Henning LN, Venditto C, Borchers MT, Barchowsky A, Weaver TE, Tichelaar JW, Prows DR, Korfhagen TR, Hardie WD, Bachurski CJ, Leikauf GD

MESH terms used to index this publication - Major topics in bold

Acute Lung Injury
Administration, Inhalation
Aerosols
Animals
Cells, Cultured
Epithelial Cells
Gene Expression Regulation
Humans
Mice
Mice, Transgenic
Nickel
Promoter Regions, Genetic
Proto-Oncogene Proteins c-jun
Pulmonary Surfactant-Associated Protein B
Respiratory Mucosa
Survival Rate
Transcription Factor AP-1
Transforming Growth Factor alpha