Linked Life Data

21239537

Source:http://linkedlifedata.com/resource/pubmed/id/21239537

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2011-5-3
pubmed:abstractText
Hypoxia-inducible factor-1? (HIF-1?), a transcription factor that functions as a master regulator of oxygen homeostasis, has been implicated in fibrinogenesis. Here, we explore the role of HIF-1? in transforming growth factor-? (TGF-?) signaling by examining the effects of TGF-?(1) on the expression of plasminogen activator inhibitor-1 (PAI-1). Immunohistochemistry of lung tissue from a mouse bleomycin (BLM)-induced pulmonary fibrosis model revealed that expression of HIF-1? and PAI-1 was predominantly induced in alveolar macrophages. Real-time RT-PCR and ELISA analysis showed that PAI-1 mRNA and activated PAI-1 protein level were strongly induced 7 days after BLM instillation. Stimulation of cultured mouse alveolar macrophages (MH-S cells) with TGF-?(1) induced PAI-1 production, which was associated with HIF-1? protein accumulation. This accumulation of HIF-1? protein was inhibited by SB431542 (type I TGF-? receptor/ALK receptor inhibitor) but not by PD98059 (MEK1 inhibitor) and SB203580 (p38 MAP kinase inhibitor). Expression of prolyl-hydroxylase domain (PHD)-2, which is essential for HIF-1? degradation, was inhibited by TGF-?(1), and this decrease was abolished by SB431542. TGF-?(1) induction of PAI-1 mRNA and its protein expression were significantly attenuated by HIF-1? silencing. Transcriptome analysis by cDNA microarray of MH-S cells after HIF-1? silencing uncovered several pro-fibrotic genes whose regulation by TGF-?(1) required HIF-1?, including platelet-derived growth factor-A. Taken together, these findings expand our concept of the role of HIF-1? in pulmonary fibrosis in mediating the effects of TGF-?(1) on the expression of the pro-fibrotic genes in activated alveolar macrophages.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1522-1504
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
300
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
L740-52
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Hypoxia-inducible factor-1? mediates TGF-?-induced PAI-1 production in alveolar macrophages in pulmonary fibrosis.
pubmed:affiliation
Department of Medicine and Biological Science, Gunma University Graduate School of Medicine, Maebashi, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't