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Updated: Jul 11, 2026
Glomerular Outgrowth as an Ex Vivo Assay to Analyze Pathways Involved in Parietal Epithelial Cell Activation
Published on: August 19, 2020
CCN3 is a novel endogenous PDGF-regulated inhibitor of glomerular cell proliferation
C R C van Roeyen1, F Eitner, T Scholl
1Department of Nephrology, RWTH Aachen University, Pauwelsstrasse 30, D-52057 Aachen, Germany.
Abstract:
CCN proteins affect cell proliferation, migration, attachment, and differentiation. We identified CCN3 as a suppressed gene following platelet-derived growth factor (PDGF)-BB or -DD stimulation in a cDNA-array analysis of mesangial cells. In vitro growth-arrested mesangial cells overexpressed and secreted CCN3, whereas the addition of the recombinant protein inhibited cell growth. Induction of mesangial cell proliferation by PDGF-BB or the specific PDGF beta-receptor ligand PDGF-DD led to downregulation of CCN3 mRNA, confirming the array study. Specific PDGF alpha-receptor ligands had no effect. CCN3 protein was found in arterial smooth muscle cells, the medullary interstitium, and occasional podocytes in the healthy rat kidney. Glomerular CCN3 was low prior to mesangial proliferation but increased as glomerular cell proliferation subsided during mesangioproliferative glomerulonephritis (GN). Inhibition of PDGF-B in mesangioproliferative disease led to overexpression of glomerular CCN3 mRNA. CCN3 localized mostly to podocytes in human glomeruli, but this expression varied widely in different human glomerulonephritides. Glomerular cell proliferation negatively correlated with CCN3 expression in necrotizing GN. Our study identifies CCN3 as an endogenous inhibitor of mesangial cell growth and a modulator of PDGF-induced mitogenesis.
Insights
CCN3 is an endogenous inhibitor of kidney cell growth. This study shows CCN3 suppresses platelet-derived growth factor (PDGF)-induced cell proliferation in mesangial cells, suggesting a role in kidney disease.
Area of Science:
- Nephrology
- Cell Biology
- Molecular Biology
Background:
- CCN proteins are key regulators of cellular processes, including proliferation and differentiation.
- Platelet-derived growth factor (PDGF) signaling pathways are implicated in kidney diseases.
Purpose of the Study:
- To investigate the role of CCN3 in mesangial cell proliferation and its regulation by PDGF.
- To determine the expression and localization of CCN3 in healthy and diseased kidneys.
Main Methods:
- cDNA-array analysis of mesangial cells stimulated with PDGF-BB and PDGF-DD.
- In vitro studies using growth-arrested mesangial cells and recombinant CCN3 protein.
- Immunohistochemical analysis of CCN3 expression in rat and human kidney tissues.
- Correlation analysis of CCN3 expression with glomerular cell proliferation in glomerulonephritis.
Main Results:
- CCN3 expression was suppressed by PDGF-BB and PDGF-DD stimulation in mesangial cells.
- Overexpression and secretion of CCN3 inhibited mesangial cell growth in vitro.
- CCN3 expression increased as glomerular cell proliferation subsided in a rat model of glomerulonephritis.
- Glomerular CCN3 expression negatively correlated with cell proliferation in human necrotizing glomerulonephritis.
Conclusions:
- CCN3 acts as an endogenous inhibitor of mesangial cell growth.
- CCN3 modulates PDGF-induced mitogenesis, suggesting a potential therapeutic target for kidney diseases.
- CCN3 expression patterns vary in different forms of glomerulonephritis.
