Document Detail

Differential effects of angiotensin II and transforming growth factor beta on the production of heparan sulfate proteoglycan by mesangial cells in vitro.
MedLine Citation:
PMID:  8829116     Owner:  NLM     Status:  MEDLINE    
This study approaches the question of whether angiotensin II (AngII) and transforming growth factor beta (TGF-beta) are important mediators for mesangial heparan sulfate proteoglycan (HSPG) production. This might explain the beneficial effects of angiotensin-converting enzyme inhibitors observed in several kidney diseases independent from their hemodynamic effects. Metabolic-labeling studies revealed that AngII induced a decrease of HSPG synthesis with decreases in N-sulfation of the glycosaminoglycan side chains. ELISA measurements with a heparan sulfate (HS)-specific monoclonal antibody confirmed that AngII decreased HS production. AngII increased TGF-beta production in a dose-dependent fashion. Specific mRNA for the large basement membrane HSPG (perlecan) decreased, whereas mRNA for TGF-beta increased after incubation with AngII. Blockade of the Subtype 1 Ang-II receptor (ATR1) reversed both the effects of AngII on HSPG and TGF-beta production. Coincubation of the mesangial cells with neutralizing antibodies against TGF-beta significantly reduced the production of HS as compared with control and AngII. These results indicate that the decrease in HS synthesis induced by AngII is not mediated by an increase in TGF-beta, but on the contrary, the increase in TGF-beta partially counteracts the inhibition of HS production by AngII. Considering the important role of HSPG in maintaining the glomerular charge barrier, cell proliferation, and matrix interaction, downregulation of the production of this molecule by increased local AngII concentrations could have important consequences, such as albuminuria and matrix expansion.
N F van Det; J T Tamsma; J van den Born; N A Verhagen; L P van den Heuvel; C W Löwik; J H Berden; J A Bruijn; M R Daha; F J van der Woude
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of the American Society of Nephrology : JASN     Volume:  7     ISSN:  1046-6673     ISO Abbreviation:  J. Am. Soc. Nephrol.     Publication Date:  1996 Jul 
Date Detail:
Created Date:  1997-03-05     Completed Date:  1997-03-05     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9013836     Medline TA:  J Am Soc Nephrol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1015-23     Citation Subset:  IM    
Department of Nephrology, Leiden University Hospital, The Netherlands.
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MeSH Terms
Angiotensin II / pharmacology*
Angiotensin-Converting Enzyme Inhibitors / pharmacology
Cells, Cultured
Gene Expression Regulation / drug effects*
Glomerular Mesangium / cytology,  metabolism*
Heparan Sulfate Proteoglycans
Heparitin Sulfate / biosynthesis*,  genetics
Oligosaccharides / metabolism
Proteoglycans / biosynthesis*,  genetics
RNA, Messenger / biosynthesis,  genetics
Receptors, Angiotensin / drug effects,  physiology
Transforming Growth Factor beta / pharmacology*
Reg. No./Substance:
0/Angiotensin-Converting Enzyme Inhibitors; 0/Heparan Sulfate Proteoglycans; 0/Oligosaccharides; 0/Proteoglycans; 0/RNA, Messenger; 0/Receptors, Angiotensin; 0/Transforming Growth Factor beta; 11128-99-7/Angiotensin II; 143972-95-6/perlecan; 9050-30-0/Heparitin Sulfate

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