Linked Life Data

18245174

Source:http://linkedlifedata.com/resource/pubmed/id/18245174

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2008-6-3
pubmed:abstractText
Enhanced transforming growth factor (TGF) -beta signaling contributes to idiopathic pulmonary fibrosis (IPF), a progressive and fatal disease characterized by alveolar epithelial type II (ATII) cell hyperplasia, (myo)fibroblast accumulation, and excessive extracellular matrix deposition. TGF-beta is a potent inducer of lung fibrosis, and it regulates the ATII cell phenotype; however, direct TGF-beta target genes controlling the ATII cell phenotype remain elusive. Here, we identified the transgelin (tagln) gene as a novel immediate target of TGF-beta/Smad3-dependent gene expression in ATII cells using a Smad3 chromatin immunoprecipitation (ChIP) screen. Direct ChIP confirmed the rapid and specific binding of Smad3 to the tagln promoter. Luciferase assays demonstrated transactivation of the tagln promoter by activin-like kinase (Alk) 5-mediated TGF-beta signaling. TGF-beta treatment resulted in rapid up-regulation of tagln, but not tagln2, mRNA and protein expression, assessed by reverse transcription-polymerase chain reaction (RT-PCR), Western blotting, and immunofluorescence. In vivo, tagln expression was significantly increased in ATII cells of mice during bleomycin-induced lung fibrosis, as well as in lung specimen obtained from IPF patients, as assessed by RT-PCR and immunohistochemistry. Knockdown of tagln using siRNA inhibited TGF-beta-induced migration of lung epithelial A549 cells, as well as primary ATII cells. We thus identified tagln as a novel target of TGF-beta/Smad3-dependent gene expression in ATII cells. Increased ATII cell expression of tagln in experimental and idiopathic pulmonary fibrosis may contribute to TGF-beta-dependent ATII cell injury, repair, and migration in lung fibrosis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1530-6860
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
22
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1778-89
pubmed:dateRevised
2011-11-10
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Transgelin is a direct target of TGF-beta/Smad3-dependent epithelial cell migration in lung fibrosis.
pubmed:affiliation
University of Giessen Lung Center, Department of Medicine II, Justus Liebig University Giessen, D-35392 Giessen, Germany.
pubmed:publicationType
Journal Article