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: Gene expression changes during the development of acute lung injury: role of transforming growth factor beta.

Authors: Wesselkamper, Scott C; Case, Lisa M; Henning, Lisa N; Borchers, Michael T; Tichelaar, Jay W; Mason, John M; Dragin, Nadine; Medvedovic, Mario; Sartor, Maureen A; Tomlinson, Craig R; Leikauf, George D

Published In Am J Respir Crit Care Med, (2005 Dec 01)

Abstract: Acute lung injury can occur from multiple causes, resulting in high mortality. The pathophysiology of nickel-induced acute lung injury in mice is remarkably complex, and the molecular mechanisms are uncertain.To integrate molecular pathways and investigate the role of transforming growth factor beta (TGF-beta) in acute lung injury in mice.cDNA microarray analyses were used to identify lung gene expression changes after nickel exposure. MAPPFinder analysis of the microarray data was used to determine significantly altered molecular pathways. TGF-beta1 protein in bronchoalveolar lavage fluid, as well as the effect of inhibition of TGF-beta, was assessed in nickel-exposed mice. The effect of TGF-beta on surfactant-associated protein B (Sftpb) promoter activity was measured in mouse lung epithelial cells.Genes that decreased the most after nickel exposure play important roles in lung fluid absorption or surfactant and phospholipid synthesis, and genes that increased the most were involved in TGF-beta signaling. MAPPFinder analysis further established TGF-beta signaling to be significantly altered. TGF-beta-inducible genes involved in the regulation of extracellular matrix function and fibrinolysis were significantly increased after nickel exposure, and TGF-beta1 protein was also increased in the lavage fluid. Pharmacologic inhibition of TGF-beta attenuated nickel-induced protein in bronchoalveolar lavage. In addition, treatment with TGF-beta1 dose-dependently repressed Sftpb promoter activity in vitro, and a novel TGF-beta-responsive region in the Sftpb promoter was identified.These data suggest that TGF-beta acts as a central mediator of acute lung injury through the alteration of several different molecular pathways.

PubMed ID: 16100012 Exiting the NIEHS site

MeSH Terms: No MeSH terms associated with this publication

Back
to Top