Document Detail

Role of fibroblast growth factor-binding protein in the pathogenesis of HIV-associated hemolytic uremic syndrome.
MedLine Citation:
PMID:  16352855     Owner:  NLM     Status:  MEDLINE    
A characteristic finding of childhood HIV-associated hemolytic uremic syndrome (HIV-HUS) is the presence of endothelial injury and microcystic tubular dilation, leading to a rapid progression of the renal disease. We have previously shown that a secreted fibroblast growth factor-binding protein (FGF-BP) is upregulated in kidneys from children affected with HIV-HUS and HIV nephropathy. Here, we sought to determine the potential role of FGF-BP in the pathogenesis of HIV-HUS. By immunohistochemical and in situ hybridization studies, we observed FGF-BP protein and mRNA upregulation in regenerating renal tubular epithelial cells from kidneys of HIV-Tg26 mice with late-stage renal disease, that is, associated with the development of microcystic tubular dilatation and accumulation of FGF-2. Moreover, FGF-BP increased the FGF-2-dependent growth and survival of cultured primary human renal glomerular endothelial cells and enhanced FGF-2-induced MAPK/ERK2 activation, as well as the proliferation of immortalized GM7373 endothelial cells. We propose that HIV-Tg26 mice are a clinically relevant model system to study the role of FGF-BP in the pathogenesis of HIV-associated renal diseases. Furthermore, the upregulation of FGF-BP by regenerating renal tubular epithelial cells may provide a mechanism by which the regenerative and angiogenic activity of FGF-2 in renal capillaries can be modulated in children with HIV-HUS and other renal disease.
Patricio E Ray; Elena Tassi; Xue-Hui Liu; Anton Wellstein
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  American journal of physiology. Regulatory, integrative and comparative physiology     Volume:  290     ISSN:  0363-6119     ISO Abbreviation:  Am. J. Physiol. Regul. Integr. Comp. Physiol.     Publication Date:  2006 Jan 
Date Detail:
Created Date:  2005-12-14     Completed Date:  2006-02-14     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  100901230     Medline TA:  Am J Physiol Regul Integr Comp Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  R105-13     Citation Subset:  IM    
Lombardi Comprehensive Cancer Center, Georgetown University, 3970 Reservoir Rd., Washington DC 20057, USA.
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MeSH Terms
Carrier Proteins / genetics,  metabolism*
Cell Line
Endothelial Cells / metabolism
Fibroblast Growth Factor 2 / metabolism
HIV Infections / complications*,  metabolism
Hemolytic-Uremic Syndrome / complications*,  metabolism*,  physiopathology
Heparitin Sulfate / metabolism
Kidney / cytology,  metabolism
Mice, Transgenic
Grant Support
Reg. No./Substance:
0/Carrier Proteins; 0/Fgfbp1 protein, mouse; 103107-01-3/Fibroblast Growth Factor 2; 139946-12-6/FGFBP1 protein, human; 9050-30-0/Heparitin Sulfate

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