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Glomerular extracellular matrix and growth factors in diffuse mesangial sclerosis
1INSERM U423, Tour Lavoisier, Hôpital Necker-Enfants Malades, Université René Descartes, 149, rue de Sèvres, 75743 Paris, France.
Pediatric Nephrology (Berlin, Germany)
|June 19, 2001
Summary
Diffuse mesangial sclerosis (DMS) involves early nephrotic syndrome and rapid glomerulosclerosis. Early GBM heparan sulfate decrease may cause proteinuria, while growth factor deregulation contributes to mesangial matrix expansion in Denys-Drash syndrome.
Area of Science:
- Nephrology
- Pathology
- Molecular Biology
Background:
- Diffuse mesangial sclerosis (DMS), isolated or in Denys-Drash syndrome (DDS), causes early nephrotic syndrome and renal failure.
- A key feature is rapid glomerulosclerosis, indicating significant extracellular matrix (ECM) accumulation.
Purpose of the Study:
- Analyze glomerular ECM antigen distribution in early DMS.
- Determine the ECM composition in mesangial areas during sclerosis.
- Investigate the expression of growth factors TGF-beta 1 and PDGFA.
Main Methods:
- Immunohistochemical analysis of glomerular ECM antigens and growth factors in DMS patients.
- Comparison of antigen distribution in early and advanced sclerotic lesions.
- Correlation of growth factor expression with disease severity.
Main Results:
- Early DMS showed decreased heparan sulfate proteoglycan (HSPG) in the glomerular basement membrane (GBM), while other ECM proteins were normally distributed.
- Advanced lesions exhibited mesangial and subendothelial accumulation of various ECM proteins, including collagens IV and VI, laminin, fibronectin, and perlecan.
- Increased expression of TGF-beta 1 and PDGFA was observed in a majority of patients.
Conclusions:
- Reduced GBM heparan sulfate may contribute to proteinuria in DMS.
- The accumulating ECM in mesangial areas is not specific in composition.
- WT1 mutation-associated deregulation of growth factors may drive rapid ECM deposition in DDS.