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Alterations in the extracellular matrix components in human glomerular diseases.
A Oomura1, T Nakamura, M Arakawa
1Department of Medicine (II), Niigata University School of Medicine, Japan.
Virchows Archiv. A, Pathological Anatomy and Histopathology
|January 1, 1989
Summary
Extracellular matrix components change in various kidney diseases. Proteinuria may stem from alterations in heparan sulfate proteoglycan (HSPG) or other anionic materials, with increased type V and VI collagens linked to mesangial sclerosis.
Area of Science:
- Nephrology
- Cell Biology
- Biochemistry
Background:
- The glomerulus, the kidney's filtering unit, relies on a complex extracellular matrix (ECM) for structural integrity and function.
- Alterations in ECM components are implicated in the pathogenesis of various glomerular diseases and proteinuria.
Purpose of the Study:
- To investigate the distribution of key ECM components, including fibronectin, laminins, collagens (types III, IV, V, VI), and heparan sulfate proteoglycan (HSPG), in normal and diseased human glomeruli.
- To correlate ECM distribution patterns with specific glomerular pathologies and proteinuria.
Main Methods:
- Indirect immunofluorescence microscopy was employed to analyze ECM distribution in 96 renal biopsies.
- Biopsies included controls and patients with minimal change nephrotic syndrome (MCNS), mesangial proliferative glomerulonephritis (PGN), membranous nephropathy (MN), and membranoproliferative glomerulonephritis (MPGN).
Main Results:
- In normal glomeruli, fibronectin, laminin, type IV collagen, and HSPG were localized to the mesangium and glomerular basement membrane (GBM). Type III collagen was primarily interstitial, while types V and VI collagens were found in mesangium, interstitium, and GBM.
- Minimal change nephrotic syndrome (MCNS) showed normal ECM distribution. Membranous nephropathy (MN) exhibited increased fibronectin, laminin, type IV collagen, and HSPG in the thickened GBM. Mesangial proliferative glomerulonephritis (PGN) showed increases in these components within the expanded mesangium.
- Membranoproliferative glomerulonephritis (MPGN) displayed elevated mesangial and GBM matrix components, with notable increases in type V and VI collagens. Type III collagen, absent in normal glomeruli, appeared in the mesangium and GBM in MPGN. HSPG levels remained unchanged in nephrotic patients.
Conclusions:
- Proteinuria in nephrotic patients may result from structural changes in the glycosaminoglycan portion of HSPG, alterations in other anionic materials, or both.
- Glomerular mesangial sclerosis is strongly associated with increased deposition of type V and VI collagens.