Document 0624
 DOCN  M95A0624
 TI    Basic fibroblast growth factor and its low affinity receptors in the
       pathogenesis of HIV-associated nephropathy in transgenic mice. American
       Pediatric Society 104th annual meeting and Society for Pediatric
       Research 63rd annual meeting; 1994 May 2-5; Seattle.
 DT    9510
 AU    Ray PE; Bruggeman LA; Weeks BE; Kopp JB; Bryant JL; Owens JW; Notkins
       AL; Klotman PE; LDB, NIDR, NIH, Bethesda, MD, USA.
 SO    Pediatr AIDS HIV Infect. 1994 Oct;5(5):318 (unnumbered abstract). Unique
       Identifier : AIDSLINE AIDS/95330420
 AB    We have established a model of HIV-associated nephropathy (HIVAN) in
       transgenic mice, using a non-infectious HIV-1 construct bearing the
       viral LTR, the env gene, and regulatory genes (PNAS 89:1577, 1992).
       Heterozygous mice develop progressive glomerulosclerosis and microcystic
       tubular dilatation in association with increased kidney weight, DNA and
       protein content. By specific immunoperoxidase staining we found
       increased expression of bFGF in the extracellular matrix surrounding
       renal tubular epithelial cells from transgenic but not in control
       kidneys. Thus, we studied the mechanisms responsible for bFGF
       accumulation in HIVAN. Release of bFGF appeared to be related to renal
       tubular cell injury as shown by electron microscopy and the presence of
       bFGF mRNA in transgenic renal tubular epithelial cells (RTEc). To
       determine whether bFGF released by injured cells remained bound to low
       affinity binding sites in transgenic kidneys, we measured bFGF binding
       sites by quantitative autoradiography. Kidneys from transgenic mice had
       increased numbers of bFGF low affinity binding sites and a markedly
       different distribution of these receptors particularly in the renal
       interstitium. Furthermore, competition binding studies of [125I]-bFGF by
       conditioned media from transgenic RTEc, produced a greater reduction in
       [125I]-bFGF binding to NIH 3T3's low affinity receptors than control
       conditioned medium. bFGF (20 ng/ml), in the absence of any other growth
       factors, induced significant proliferation of transgenic RTEc. These
       studies suggest that bFGF and its low affinity receptors may play an
       important role in the stimulation of interstitial proliferation and
       microcyst formation in HIVAN.
 DE    Animal  AIDS-Associated Nephropathy/*METABOLISM/PATHOLOGY  Fibroblast
       Growth Factor, Basic/*METABOLISM  *HIV-1  Kidney/METABOLISM/PATHOLOGY
       Mice  Mice, Transgenic  Receptors, Fibroblast Growth Factor/*METABOLISM
       MEETING ABSTRACT  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).