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Platelet-derived growth factor expression in mesangial proliferative glomerulonephritis
L Gesualdo1, M Pinzani, J J Floriano
1Institute of Pathology, Veterans Administration Hospital, Case Western Reserve University, Cleveland, Ohio.
Abstract:
Proliferation of mesangial cells and expansion of mesangial matrix are common histologic features of proliferative glomerular disease, a frequent cause of renal failure. Proliferation of glomerular mesangial cells occurs in response to platelet-derived growth factor (PDGF), and these cells release PDGF and express PDGF A and B chain mRNAs. However, all studies relating PDGF to potential changes in glomerular structure and function to date have been performed in vitro. To explore the role of PDGF in proliferative glomerulonephritides, we studied the expression of PDGF in vivo in two animal models of IgA nephropathy with different histologic patterns of glomerular injury: either predominant mesangial proliferation or expansion of mesangial matrix. Increased expression of PDGF and PDGF B-chain mRNA in whole kidneys from diseased mice was demonstrated by immunohistochemical techniques and by solution hybridization assay, respectively. Immunohistochemically, PDGF was localized primarily within the mesangial area of glomeruli and to a much lower extent in interstitium. The increased PDGF expression correlated with the degree of hypercellularity and clinical features of the disease. In addition, PDGF expression was increased in some forms of human glomerulonephritis, characterized by mesangial proliferation. These findings suggest that PDGF may be a major contributor to mesangial cell proliferation seen in proliferative glomerulonephritides.
Insights
Platelet-derived growth factor (PDGF) drives mesangial cell proliferation in proliferative glomerulonephritis. This study demonstrates increased PDGF expression in animal models and human kidney disease, linking it to kidney damage.
Area of Science:
- Nephrology
- Molecular Biology
- Pathology
Background:
- Proliferative glomerular diseases cause renal failure via mesangial cell proliferation and matrix expansion.
- Platelet-derived growth factor (PDGF) is known to stimulate mesangial cell proliferation.
- Previous studies on PDGF's role were limited to in vitro settings.
Purpose of the Study:
- To investigate the in vivo role of PDGF in proliferative glomerulonephritides.
- To examine PDGF expression in animal models of IgA nephropathy.
- To correlate PDGF levels with specific histologic patterns and disease severity.
Main Methods:
- Utilized two animal models of IgA nephropathy with distinct glomerular injury patterns.
- Assessed PDGF and PDGF B-chain mRNA expression using immunohistochemistry and solution hybridization.
- Examined PDGF expression in human glomerulonephritis cases.
Main Results:
- Demonstrated increased PDGF and PDGF B-chain mRNA expression in diseased mouse kidneys.
- Localized increased PDGF primarily to the glomerular mesangium.
- Found a correlation between elevated PDGF expression, glomerular hypercellularity, and clinical disease features.
Conclusions:
- PDGF is upregulated in vivo during proliferative glomerulonephritis.
- Increased PDGF expression is associated with mesangial cell proliferation and disease severity.
- PDGF is implicated as a key factor in the pathogenesis of proliferative glomerulonephritides.