Document Detail


Regulation of fibrillin-1 by biglycan and decorin is important for tissue preservation in the kidney during pressure-induced injury.
MedLine Citation:
PMID:  15277214     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
There is growing evidence that the two small leucine-rich proteoglycans biglycan and decorin regulate the assembly of connective tissues and alter cell behavior during development and pathological processes. In this study, we have used an experimental animal model of unilateral ureteral ligation and mice deficient in either biglycan or decorin. We discovered that pressure-induced injury to the wild-type kidneys led to overexpression of decorin, biglycan, fibrillin-1, and fibrillin-2. In contrast, in biglycan-deficient kidneys the overexpression of fibrillin-1 was markedly attenuated and this was associated with cystic dilatation of Bowman's capsule and proximal tubules. Notably, we found that in ligated kidneys from decorin-null mice, fibrillin-1 expression was initially enhanced to the same extent as in wild-type animals. However, long-term obstruction resulted in down-regulation of fibrillin-1 and concurrent cystic dilatation of Bowman's capsule in 33% of kidneys at 5 months after obstruction. In all of the genotypes, no differences in fibrillin-2 expression were observed. These in vivo data correlated with a significant induction of fibrillin-1 expression in renal fibroblasts and mesangial cells by recombinant biglycan and decorin. Our results indicate a novel role for decorin and biglycan during pressure-induced renal injury by stimulating fibrillin-1 expression.
Authors:
Liliana Schaefer; Daniel Mihalik; Andrea Babelova; Miroslava Krzyzankova; Hermann-Josef Gröne; Renato V Iozzo; Marian F Young; Daniela G Seidler; Guoqing Lin; Dieter P Reinhardt; Roland M Schaefer
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The American journal of pathology     Volume:  165     ISSN:  0002-9440     ISO Abbreviation:  Am. J. Pathol.     Publication Date:  2004 Aug 
Date Detail:
Created Date:  2004-07-27     Completed Date:  2004-08-24     Revised Date:  2013-06-09    
Medline Journal Info:
Nlm Unique ID:  0370502     Medline TA:  Am J Pathol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  383-96     Citation Subset:  AIM; IM    
Affiliation:
Medizinische Klinik und Poliklinik D, Albert-Schweitzer-Str. 33, 48149 Münster, Germany. schaefl@uni-muenster.de
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MeSH Terms
Descriptor/Qualifier:
Animals
Biglycan
Decorin
Disease Models, Animal
Extracellular Matrix Proteins / metabolism
Fibroblasts / cytology,  metabolism
Fibrosis / genetics,  pathology
Gene Expression Regulation*
Genotype
Glomerular Mesangium / cytology,  metabolism
Heterozygote
Homozygote
Kidney / injuries*,  metabolism*,  pathology
Mice
Mice, Knockout
Microfilament Proteins / metabolism*
Pressure / adverse effects
Proteoglycans / genetics,  physiology*
Transforming Growth Factor beta / antagonists & inhibitors
Grant Support
ID/Acronym/Agency:
R01 CA39481/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Bgn protein, mouse; 0/Biglycan; 0/Dcn protein, mouse; 0/Decorin; 0/Extracellular Matrix Proteins; 0/Microfilament Proteins; 0/Proteoglycans; 0/Transforming Growth Factor beta; 0/fibrillin
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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