Linked Life Data

21209004

Source:http://linkedlifedata.com/resource/pubmed/id/21209004

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2011-4-5
pubmed:abstractText
Increasing evidence suggests that chronic kidney disease may develop following acute kidney injury and that this may be due, in part, to hypoxia-related phenomena. Hypoxia-inducible factor (HIF) is stabilized in hypoxic conditions and regulates multiple signaling pathways that could contribute to renal fibrosis. As transforming growth factor (TGF)-? is known to mediate renal fibrosis, we proposed a profibrotic role for cross talk between the TGF-?1 and HIF-1? signaling pathways in kidney cells. Hypoxic incubation increased HIF-1? protein expression in cultured human renal tubular epithelial cells and mouse embryonic fibroblasts. TGF-?1 treatment further increased HIF-1? expression in cells treated with hypoxia and also increased HIF-1? in normoxic conditions. TGF-?1 did not increase HIF-1? mRNA levels nor decrease the rate of protein degradation, suggesting that it enhances normoxic HIF-1? translation. TGF-? receptor (ALK5) kinase activity was required for increased HIF-1? expression in response to TGF-?1, but not to hypoxia. A dominant negative Smad3 decreased the TGF-?-stimulated reporter activity of a HIF-1?-sensitive hypoxia response element. Conversely, a dominant negative HIF-1? construct decreased Smad-binding element promoter activity in response to TGF-?. Finally, blocking HIF-1? transcription with a biochemical inhibitor, a dominant negative construct, or gene-specific knockdown decreased basal and TGF-?1-stimulated type I collagen expression, while HIF-1? overexpression increased both. Taken together, our data demonstrate cooperation in signaling between Smad3 and HIF-1? and suggest a new paradigm in which HIF-1? is necessary for normoxic, TGF-?1-stimulated renal cell fibrogenesis.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1522-1466
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
300
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
F898-905
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Interdependence of HIF-1? and TGF-?/Smad3 signaling in normoxic and hypoxic renal epithelial cell collagen expression.
pubmed:affiliation
Divisions of Critical Care, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural