Role of fibroblast growth factor-binding protein in the pathogenesis of HIV-associated hemolytic uremic syndrome

2006 ◽  
Vol 290 (1) ◽  
pp. R105-R113 ◽  
Author(s):  
Patricio E. Ray ◽  
Elena Tassi ◽  
Xue-Hui Liu ◽  
Anton Wellstein
Keyword(s):  
Endothelial Cells ◽  
Growth Factor ◽  
Renal Disease ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth ◽  
Tubular Epithelial Cells ◽  
Renal Tubular Epithelial Cells ◽  
Uremic Syndrome ◽  
Renal Tubular

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.

Cross talk between primary human renal tubular cells and endothelial cells in cocultures

2012 ◽  
Vol 302 (8) ◽  
pp. F1055-F1062 ◽  
Author(s):  
Farah Tasnim ◽  
Daniele Zink
Keyword(s):  
Endothelial Cells ◽  
Growth Factor ◽  
Epithelial Cells ◽  
Renal Disease ◽  
Cross Talk ◽  
Tubular Epithelial Cells ◽  
Renal Tubular Epithelial Cells ◽  
Tubular Cells ◽  
Renal Tubular

Interactions between renal tubular epithelial cells and adjacent endothelial cells are essential for normal renal functions but also play important roles in renal disease and repair. Here, we investigated cocultures of human primary renal proximal tubular cells (HPTC) and human primary endothelial cells to address the cross talk between these cell types. HPTC showed improved proliferation, marker gene expression, and enzyme activity in cocultures. Also, the long-term maintenance of epithelia formed by HPTC was improved, which was due to the secretion of transforming growth factor-β1 and its antagonist α2-macroglobulin. HPTC induced endothelial cells to secrete increased amounts of these factors, which balanced each other functionally and only displayed in combination the observed positive effects. In addition, in the presence of HPTC endothelial cells expressed increased amounts of hepatocyte growth factor and vascular endothelial growth factor, which have well-characterized effects on renal tubular epithelial cells as well as on endothelial cells. Together, the results showed that HPTC stimulated endothelial cells to express a functionally balanced combination of various factors, which in turn improved the performance of HPTC. The results give new insights into the cross talk between renal epithelial and endothelial cells and suggest that cocultures could be also useful models for the analysis of cellular communication in renal disease and repair. Furthermore, the characterization of defined microenvironments, which positively affect HPTC, will be helpful for improving the performance of this cell type in in vitro applications including in vitro toxicology and kidney tissue engineering.

Role of basic fibroblast growth factor in the pathogenesis of moyamoya disease

1998 ◽  
Vol 5 (5) ◽  
pp. E4 ◽  
Author(s):  
Kiyohiro Houkin ◽  
Tetsuyuki Yoshimoto ◽  
Hiroshi Abe ◽  
Kazuo Nagashima ◽  
Masahumi Nagashima ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Basic Fibroblast Growth Factor ◽  
Moyamoya Disease ◽  
Fibroblast Growth ◽  
Apoptotic Process ◽  
Fragmented Dna ◽  
The Media

The pathogenesis of moyamoya disease is still under investigation. In this study, the authors focus on the role of cytokines in the pathogenesis of moyamoya disease by using immunohistochemical analyses. The authors examined two specimens in the circle of Willis obtained at autopsy from two patients with moyamoya disease and two additional specimens obtained from control cadavers with atherosclerotic stenosis of the intracranial carotid arteries. Immunohistochemical examinations of the sections of the major intracranial arteries were performed using antismooth muscle cells (SMCs), monocytes, growth factor, cell nuclear antigen, and fragmented DNA antibodies. Basic fibroblast growth factor (bFGF) staining was present only in the endothelial cells of the moyamoya disease specimens and was not seen in control samples. In addition, the endothelial cells and SMCs in the media were positive for terminal deoxynucleotidyl transferase-mediated biotinylated deoxyuridine triphosphate nick-end labeling of fragmented DNA method but not in the SMCs in the intima in moyamoya disease specimens, which indicates that an apoptotic process is active in only SMCs in the media but not in the intima. In conclusion, it is suggseted that the presence of bFGF in the media specifically seen in moyamoya disease suppresses the apoptotic process of SMCs in the intima.

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