Linked Life Data

15047707

Source:http://linkedlifedata.com/resource/pubmed/id/15047707

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
22
pubmed:dateCreated
2004-5-24
pubmed:abstractText
Bone morphogenetic protein-7 (BMP7) is expressed in adult kidney and reduces renal fibrogenesis when given exogenously to rodents with experimental chronic nephropathies. In mesangial cells that regulate glomerular fibrosis in vivo, BMP7 inhibits transforming growth factor beta (TGF-beta)-driven fibrogenesis, primarily by preventing the TGF-beta-dependent down-regulation of matrix degradation and up-regulation of PAI-1. The signals and mechanisms of the BMP7 opposition to actions of TGF-beta are unknown. Here we show in mesangial cells that BMP7 reduces nuclear accumulation of Smad3 and blocks the transcriptional up-regulation of the TGF-beta/Smad3 target, CAGA-lux. Smad5 knock-down impairs the ability of BMP7 to interfere with the activation of CAGA-lux and the accumulation of PAI-1 by TGF-beta indicating that Smad5 is required. Smad5 knock-down also reduces the rise in Smad6 upon BMP7. Forced expression of smad5 (found to be the preferred BMP7-induced receptor-activated Smad signal in mesangial cells) or of smad6 mimics BMP7 in opposing the increase in transcriptional activation of PAI-1 and its secretion upon TGF-beta. This suggests a model for the BMP7-induced opposition to TGF-beta-dependent mesangial fibrogenesis requiring Smad5; the model involves the inhibitory Smad6 downstream of Smad5 as well as reduced availability of Smad3 in the nucleus. BMP7 does not require signaling through Erk1/2, p38, or JNK and does not utilize the TGF-beta transcriptional co-repressors Ski or SnoN in mesangial cells. These studies provide first insights into mechanisms through which BMP7 opposes TGF-beta-induced glomerular fibrogenesis.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
28
pubmed:volume
279
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
23200-6
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Bone morphogenetic protein-7 signals opposing transforming growth factor beta in mesangial cells.
pubmed:affiliation
Harbor-UCLA Research and Education Institute, UCLA, Torrance, California 90502, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't