Document Detail

Modulator of bone morphogenetic protein activity in the progression of kidney diseases.
MedLine Citation:
PMID:  16871237     Owner:  NLM     Status:  MEDLINE    
Tubular damage and interstitial fibrosis is a final common pathway leading to end-stage renal disease, and once tubular damage is established, it cannot be reversed by currently available treatment. The administration of bone morphogenetic protein-7 (BMP-7) in pharmacological doses repairs established tubular damages and improves renal function in several kidney disease models; however, pathophysiological role of endogenous BMP-7 and regulatory mechanism of its activities remain elusive. The activity of BMP is precisely regulated by certain classes of molecules termed BMP agonist/antagonist. In this review, roles of BMP agonist/antagonists possibly modulating the activity of BMP in kidney diseases are discussed. Our group demonstrated that uterine sensitization-associated gene-1 (USAG-1), a novel BMP antagonist abundantly expressed in the kidney, is the central negative regulator of BMP-7 in the kidney, and that mice lacking USAG-1 (USAG-1(-/-) mice) are resistant to kidney injuries. USAG-1(-/-) mice exhibited markedly prolonged survival and preserved renal function in acute and chronic renal injuries. Renal BMP signaling, assessed by phosphorylation of Smad proteins, is significantly enhanced in USAG-1(-/-) mice during renal injury, indicating that the preservation of renal function is attributed to enhancement of endogenous BMP-7 signaling. Furthermore, the administration of neutralizing antibody against BMP-7 abolished renoprotection in USAG-1(-/-) mice, indicating that USAG-1 plays a critical role in the modulation of renoprotective action of BMP, and that inhibition of USAG-1 will be promising means of development of novel treatment for kidney diseases.
M Yanagita
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review     Date:  2006-07-26
Journal Detail:
Title:  Kidney international     Volume:  70     ISSN:  0085-2538     ISO Abbreviation:  Kidney Int.     Publication Date:  2006 Sep 
Date Detail:
Created Date:  2006-09-07     Completed Date:  2006-10-17     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0323470     Medline TA:  Kidney Int     Country:  United States    
Other Details:
Languages:  eng     Pagination:  989-93     Citation Subset:  IM    
COE Formation for Genomic Analysis of Disease Model Animals with Multiple Genetic Alterations, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
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MeSH Terms
Bone Morphogenetic Proteins / antagonists & inhibitors*,  genetics,  metabolism
Disease Progression
Kidney Diseases / etiology,  pathology*
Mice, Knockout
Models, Biological
Signal Transduction
Smad Proteins / metabolism
Reg. No./Substance:
0/Bone Morphogenetic Proteins; 0/Smad Proteins; 0/Sostdc1 protein, mouse

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