Source:http://linkedlifedata.com/resource/pubmed/id/16672319
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
6
|
| pubmed:dateCreated |
2006-5-24
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| pubmed:abstractText |
Podocyte apoptosis initiates progressive glomerulosclerosis in TGF-beta1 transgenic and CD2AP-knockout (CD2AP-/-) mice. It was previously shown that in both mouse models, activation of the TGF-beta pathway is the key event during development of podocyte apoptosis. Furthermore, CD2AP is an important modifier of TGF-beta-induced survival signaling via activation of the phosphoinositol 3-kinase/AKT signaling pathway. This article presents IGF-binding protein-3 (IGFBP-3) as a new modulator of apoptosis and survival signaling in glomerular podocytes. High expression of IGFBP-3 protein in the urine of diseased CD2AP-/- mice was discovered, and IGFBP-3 expression in glomerular podocytes and parietal cells was detected. IGFBP-3 can induce changes in podocyte actin cytoskeleton, leads to apoptosis in cultured murine podocytes, and can enhance TGF-beta1-induced apoptosis in vitro. For studying this process on a molecular level, proapoptotic p38 mitogen-activated protein kinase pathways and antiapoptotic phosphoinositol 3-kinase/AKT pathways were examined in cultured murine podocytes. It was found that IGFBP-3 increments the level of TGF-beta1-induced phosphorylated p38 mitogen-activated protein kinase and decreases the phosphorylation of antiapoptotic AKT. This effect is specific for the co-stimulation of IGFBP-3 with TGF-beta1 because a combination of IGFBP-3 with bone morphogenic protein-7 (BMP-7), another member of the TGF-beta superfamily, results in apoptosis opposing signaling effects with a strong increase of phosphorylated AKT and subsequent functional effects. These results demonstrate that the IGF/IGFBP axis plays an important role in the development of podocyte apoptosis by modulation of TGF-beta and BMP-7-induced pro- and antiapoptotic signals.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical | |
| pubmed:status |
MEDLINE
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| pubmed:month |
Jun
|
| pubmed:issn |
1046-6673
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| pubmed:author |
pubmed-author:AchenbachJohannesJ,
pubmed-author:HallerHermannH,
pubmed-author:MengelMichaelM,
pubmed-author:ParkJoon-KeunJK,
pubmed-author:PaschyMelanieM,
pubmed-author:PetersImkeI,
pubmed-author:SchifferMarioM,
pubmed-author:TossidouIriniI,
pubmed-author:WoronieckiRobertR,
pubmed-author:de GrootKirstenK
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| pubmed:issnType |
Print
|
| pubmed:volume |
17
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
1644-56
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| pubmed:meshHeading |
pubmed-meshheading:16672319-Adolescent,
pubmed-meshheading:16672319-Adult,
pubmed-meshheading:16672319-Aged,
pubmed-meshheading:16672319-Animals,
pubmed-meshheading:16672319-Bone Morphogenetic Proteins,
pubmed-meshheading:16672319-Child,
pubmed-meshheading:16672319-Child, Preschool,
pubmed-meshheading:16672319-Female,
pubmed-meshheading:16672319-Glomerulosclerosis, Focal Segmental,
pubmed-meshheading:16672319-Humans,
pubmed-meshheading:16672319-Insulin-Like Growth Factor Binding Protein 3,
pubmed-meshheading:16672319-Male,
pubmed-meshheading:16672319-Mice,
pubmed-meshheading:16672319-Mice, Knockout,
pubmed-meshheading:16672319-Middle Aged,
pubmed-meshheading:16672319-Podocytes,
pubmed-meshheading:16672319-Signal Transduction,
pubmed-meshheading:16672319-Transforming Growth Factor beta
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| pubmed:year |
2006
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| pubmed:articleTitle |
IGF-binding protein-3 modulates TGF-beta/BMP-signaling in glomerular podocytes.
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| pubmed:affiliation |
Division of Nephrology, Department of Medicine, Hannover Medical School, Carl-Neuberg-Strasse 1, Hannover, 30625 Germany, and Division of Pediatric Nephrology, Children's Hospital at Montefiore, Bronx, NY, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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