Role of fibroblast growth factor-binding protein in the pathogenesis of HIV-associated hemolytic uremic syndrome.
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.
Ray
Patricio E
PE
Lombardi Comprehensive Cancer Center, Georgetown University, 3970 Reservoir Rd., Washington DC 20057, USA.
Tassi
Elena
E
Liu
Xue-Hui
XH
Wellstein
Anton
A
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D042783:Endothelial Cells / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D015658:HIV Infections / Q000150:complications* / Q000378:metabolism; D006463:Hemolytic-Uremic Syndrome / Q000150:complications* / Q000378:metabolism* / Q000503:physiopathology; D006497:Heparan Sulfate / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D007668:Kidney / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D015854:Up-Regulation
D002352:Carrier Proteins; D016222:Fibroblast Growth Factor 2; D006497:Heparan Sulfate; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; C489453:Fgfbp1 protein, mouse; C070699:FGFBP1 protein, human