1992 Fiscal Year Final Research Report Summary
Glomerular basement membrane permeability factor in minimal change nephrotic syndrome
| Project/Area Number |
02670440
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Pediatrics
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| Research Institution | Kobe University |
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Principal Investigator |
YOSHIKAWA Norishige Kobe University School of Medicine, Associate Professor, 医学部, 助教授 (10158412)
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| Project Period (FY) |
1990 – 1992
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| Keywords | minimal change nephrotic syndrome / glomerular basement membrane permeability / proteinuria / peripheral blood mononuclear cell / anionic sites / vascular permeability factor / Northern blot analysis / mesangial cells |
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| Research Abstract |
Minimal change nephrotic syndrome(MCNS)is the most common form of nephrotic syndrome in children. However, the pathogenesis of MCNS remains unknown. Several investigators have been proposed suggesting that MCNS is immune-mediated disorder. Shalhoub postulated that lymphocytes in patients with MCNS produce a lymphokine that causes increased permeability of the glomerular basement membrane(GBM), resulting in proteinuria and nephrotic syndrome.
Supernatants of peripheral blood mononuclear cell culture from children with MCNS were tested for their ability to increase GBM permeability and for effects on anionic sites in the GBM. Supernatants from cultures of concanavalin A-stimulated peripheral blood mononuclear cells from patients with MCNS were infused into the renal arteries of normal rats. Infusion caused a significant reduction of anionic sites in the GBM and a significant increase in urinary albumin excretion. These findings show that stimulation of peripheral blood mononuclear cells from MCNS results in liberation of soluble substances which reduce polyanions in the GBM and increase GBM permeability.
Recently vascular permeability factor(VPF)has been purified from human lymphoma line. VPF increases fluid permeability from blood vessels. Northern blot analysis revealed that human peripheral blood mononuclear cells and glomerular mesangial cells expressed VPF mRNA. VPF protein was also detected in human mesangial cells. VPF infusion into rats resulted in a dosedependent increase in urinary albumin excretion. These findings indicate that mesangial cells and peripheral blood mononuclear cells produce VPF and VPF released from these cells induces albuminuria in MCNS.
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