Up-regulation of a fibroblast growth factor binding protein in children with renal diseases.
BACKGROUND
Basic fibroblast growth factor (bFGF) is an angiogenic growth factor that is involved in renal growth and the pathogenesis of renal diseases. We have detected high levels of bFGF accumulated in the kidney of HIV-transgenic mice and in children with HIV-associated renal diseases and the hemolytic uremic syndrome (HUS). However, the mechanism modulating the activity of bFGF under these circumstances is poorly understood. We carried out experiments to determine whether a secreted binding protein (FGF-BP) that modulates the activity of bFGF during the process of tumor growth was expressed in pediatric kidneys and to define whether the expression of FGF-BP was altered in pediatric renal diseases associated with high levels of bFGF.


METHODS
Immunohistochemistry and in situ hybridization studies were done in 41 renal sections from children with HIV nephropathies, HUS, other pediatric renal diseases, controls, and fetal kidneys. Western blots and reverse transcriptase-polymerase chain reaction studies were done in selected urine samples and cultured renal cells. Recombinant FGF-BP was produced to study the mitogenic activity of FGF-BP in cultured human renal proximal tubular epithelial cells (RPTEcs).


RESULTS
The expression of FGF-BP was up-regulated predominately in renal tubular epithelial cells in children with renal tubular injury, HIV-associated nephropathy (HIVAN), and HUS, and FGF-BP was secreted in the urine of these patients. FGF-BP was also abundantly expressed in developing fetal renal tubules. Recombinant FGF-BP enhanced the mitogenic effects of bFGF in cultured human RPTEcs.


CONCLUSIONS
The localization of FGF-BP in renal tubular epithelial cells could provide a mechanism by which the activity of bFGF is modulated in developing and regenerating renal tubules of children.
Liu
X H
XH
Children's Research Institute, Research Center for Molecular Physiology, Children's National Medical Center, Washington DC 20010, USA.
Aigner
A
A
Wellstein
A
A
Ray
P E
PE
D016263:AIDS-Associated Nephropathy / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D016022:Case-Control Studies; D002478:Cells, Cultured; D002648:Child; D017931:DNA Primers / Q000235:genetics; D005333:Fetus / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D006463:Hemolytic-Uremic Syndrome / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D007674:Kidney Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism; D015854:Up-Regulation
D002352:Carrier Proteins; D017931:DNA Primers; C489453:Fgfbp1 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D016222:Fibroblast Growth Factor 2; C070699:FGFBP1 protein, human; D013936:Thymidine