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.
journal_name
Am J Respir Cell Mol Biolauthors
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 GDdoi
10.1165/rcmb.2008-0317OCsubject
Has Abstractpub_date
2009-08-01 00:00:00pages
226-36issue
2eissn
1044-1549issn
1535-4989pii
2008-0317OCjournal_volume
41pub_type
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