Decorin-mediated regulation of fibrillin-1 in the kidney involves the insulin-like growth factor-I receptor and Mammalian target of rapamycin.

Decorin-mediated regulation of fibrillin-1 in the kidney involves the insulin-like growth factor-I receptor and Mammalian target of rapamycin. Research Abstract Details 

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Decorin-mediated regulation of fibrillin-1 in the kidney involves the insulin-like growth factor-I receptor and Mammalian target of rapamycin. Abstract Text:

Liliana Schaefer,Wasiliki Tsalastra,Andrea Babelova,Martina Baliova,Jens Minnerup,Lydia Sorokin,Hermann-Josef ,Dieter P Reinhardt,Josef Pfeilschifter,Renato V Iozzo,Roland M Schaefer,

Decorin, a small leucine-rich proteoglycan, affects the synthesis of the elastic fiber component fibrillin-1 in the kidney via hitherto unknown mechanisms. Here, we show that decorin binds to and induces phosphorylation of insulin-like growth factor-I (IGF-I) receptor in renal fibroblasts. Inhibition of the IGF-I receptor tyrosine kinase and its downstream target phosphoinositide-3 kinase prevented decorin-mediated synthesis of fibrillin-1. Furthermore, decorin induced phosphorylation of phosphoinositide-dependent kinase 1, protein kinase B/Akt, mammalian target of rapamycin (mTOR), and p70 S6 kinase. Accordingly, the enhanced synthesis of fibrillin-1 was blocked by rapamycin, an inhibitor of mTOR. Notably, IGF-I, which signals through the same pathway, also stimulated fibrillin-1 synthesis. Systemic administration of rapamycin to mice subjected to unilateral ureteral obstruction, a model of renal fibrosis and increased fibrillin-1 synthesis, markedly reduced the number of interstitial fibroblasts and fibrillin-1 deposition. In streptozotocin-induced diabetes, IGF-I receptor was up-regulated in the kidneys from decorin-null mice. However, this could not compensate for the decorin deficiency, resulting ultimately in decreased fibrillin-1 content. This study provides evidence for the involvement of decorin and the IGF-I receptor/mTOR/p70 S6 kinase signaling pathway in the translational regulation of fibrillin-1.

Decorin-mediated regulation of fibrillin-1 in the kidney involves the insulin-like growth factor-I receptor and Mammalian target of rapamycin. Publishing Authors By Initials

L Schaefer,W Tsalastra,A Babelova,M Baliova,J Minnerup,L Sorokin,HJ ,DP Reinhardt,J Pfeilschifter,RV Iozzo,RM Schaefer,

For similar organic chemicals: lactones: macrolides: sirolimus research abstracts see: organic chemicals: lactones: macrolides: sirolimus research

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Decorin-mediated regulation of fibrillin-1 in the kidney involves the insulin-like growth factor-I receptor and Mammalian target of rapamycin. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: The American journal of pathology

VOLUME: 170

Page Numbers: 301-15

Journal Abbreviation: Am. J. Pathol.

ISSN: 0002-9440

DAY: 3

MONTH: Jan

YEAR: 2007

Decorin-mediated regulation of fibrillin-1 in the kidney involves the insulin-like growth factor-I receptor and Mammalian target of rapamycin. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 370502

Decorin-mediated regulation of fibrillin-1 in the kidney involves the insulin-like growth factor-I receptor and Mammalian target of rapamycin. Keywords Mesh Terms:

KEYWORDS: Sirolimus

MESH TERMS: pharmacology

Chemical & Substance for Abstract: Decorin-mediated regulation of fibrillin-1 in the kidney involves the insulin-like growth factor-I receptor and Mammalian target of rapamycin. Information

Substance Name: Protein Kinases

Registry Number: EC 2.7.1.37

Grant and Affiliation Information for Decorin-mediated regulation of fibrillin-1 in the kidney involves the insulin-like growth factor-I receptor and Mammalian target of rapamycin.

AFFILIATION: Departments of Internal Medicine D, University of Münster, Münster, Germany. schaefer@med.uni-frankfurt.de

Country: United States

AGENCY: United States NCI

GRANT: CA47282

ACRONYM: CA

MEDLINETA: Am J Pathol

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