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PMID:19251946

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Citation

Vuga, LJ, Ben-Yehudah, A, Kovkarova-Naumovski, E, Oriss, T, Gibson, KF, Feghali-Bostwick, C and Kaminski, N (2009) WNT5A is a regulator of fibroblast proliferation and resistance to apoptosis. Am. J. Respir. Cell Mol. Biol. 41:583-9

Abstract

Usual interstitial pneumonia (UIP) is a specific histopathologic pattern of interstitial lung fibrosis that may be idiopathic or secondary to autoimmune diseases and environmental exposures. In this study, we compared gene expression patterns in primary fibroblasts isolated from lung tissues with UIP histology and fibroblasts isolated from lung tissues with normal histology using expression microarrays. We found that WNT5A was significantly increased in fibroblasts obtained from UIP lung tissues compared with normal lung fibroblasts, an observation verified by quantitative real-time RT-PCR and Western blot. Because the role of WNT5A in UIP is unknown, we treated normal lung fibroblasts or UIP lung fibroblasts with WNT5A, and found that WNT5A increased proliferation as well as relative resistance to H2O2-induced apoptosis. This effect was not mediated through the canonical WNT/beta-catenin pathway, as WNT5A induced a decrease in beta-catenin levels in the same cells. In addition, WNT5A induced increases in fibronectin and alpha(5)-integrin in normal lung fibroblasts. Collectively, our data suggest that WNT5A may play a role in fibroblast expansion and survival characteristics of idiopathic pulmonary fibrosis and other fibrotic interstitial lung diseases that exhibit UIP histological patterns.

Links

PubMed PMC2778165 Online version:10.1165/rcmb.2008-0201OC

Keywords

Animals; Apoptosis/drug effects; Blotting, Western; Case-Control Studies; Caspase 3/metabolism; Cell Line; Cell Proliferation; Cell Survival; Fibroblasts/drug effects; Fibroblasts/metabolism; Fibroblasts/pathology; Fibronectins/metabolism; Gene Expression Profiling/methods; Humans; Hydrogen Peroxide/toxicity; Idiopathic Pulmonary Fibrosis/genetics; Idiopathic Pulmonary Fibrosis/metabolism; Idiopathic Pulmonary Fibrosis/pathology; Integrin alpha5/metabolism; Lung/metabolism; Lung/pathology; Mice; Oligonucleotide Array Sequence Analysis; Proto-Oncogene Proteins/genetics; Proto-Oncogene Proteins/metabolism; RNA Interference; Recombinant Proteins/metabolism; Reverse Transcriptase Polymerase Chain Reaction; Transfection; Up-Regulation; Wnt Proteins/genetics; Wnt Proteins/metabolism; beta Catenin/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:WNT5A

involved_in

GO:0043066: negative regulation of apoptotic process

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:WNT5A

involved_in

GO:0048146: positive regulation of fibroblast proliferation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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