bFGF and its low affinity receptors in the pathogenesis of HIV-associated nephropathy in transgenic mice.
HIV-associated nephropathy is characterized by extensive tubulointerstitial disease with epithelial cell injury, microcystic proliferation, and tubular regeneration with glomerulosclerosis. To explore the role of bFGF as a mediator of HIV-induced interstitial disease, we utilized an HIV transgenic mouse model that manifests clinical and histological features observed in patients. In transgenic mice, simultaneous renal epithelial cell proliferation and injury were detected in vivo. In areas of microcystic proliferation, immunoreactive bFGF colocalized with extracellular matrix. Kidneys from transgenic mice had increased bFGF low affinity binding sites, particularly in the renal interstitium. In vitro, transgenic renal tubular epithelial cells proliferated more rapidly and generated tubular structures spontaneously, in marked contrast to nontransgenic renal cells where these pathologic features could be mimicked by exogenous bFGF. These studies suggest that renal bFGF and its receptors play an important role in the pathogenesis of HIV-associated nephropathy.
Ray
P E
PE
Viral Pathogenesis Unit, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland.
Bruggeman
L A
LA
Weeks
B S
BS
Kopp
J B
JB
Bryant
J L
JL
Owens
J W
JW
Notkins
A L
AL
Klotman
P E
PE
D016263:AIDS-Associated Nephropathy / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D001345:Autoradiography; D002455:Cell Division; D004247:DNA / Q000032:analysis; D004195:Disease Models, Animal; D004848:Epithelium / Q000473:pathology; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D005923:Glomerulosclerosis, Focal Segmental / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D015497:HIV-1; D007124:Immunoenzyme Techniques; D007684:Kidney Tubules / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D009395:Nephritis, Interstitial / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism*
D017468:Receptors, Fibroblast Growth Factor; D016222:Fibroblast Growth Factor 2; D004247:DNA