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Mesangial cells express PDGF mRNAs and proliferate in response to PDGF
P J Shultz1, P E DiCorleto, B J Silver
1Department of Medicine, Veterans Administration Medical Center, Cleveland, Ohio.
Abstract:
Platelet-derived growth factor (PDGF) is a potent mitogen for cells of mesenchymal origin and is released and/or synthesized by platelets, macrophages, endothelial cells, and rat mesangial cells. In the present investigation, we found that human glomerular mesangial cells in culture release a PDGF-like protein which competes for 125I-PDGF binding to human foreskin fibroblasts and is mitogenic for these fibroblasts. The competing and to a lesser extent the mitogenic activities present in the conditioned medium are partially recognized by an anti-PDGF antibody. Northern blot analysis of poly(A)+ RNA from human mesangial cells demonstrates the expression of both PDGF A- and B-chain mRNAs. PDGF also binds to mesangial cells in a specific manner and stimulates DNA synthesis and cell proliferation. These data suggest that a PDGF-like protein secreted by mesangial cells or released from platelets, monocytes, or endothelial cells during glomerular inflammation may function as an autocrine or a paracrine growth factor for these cells. The biological role of PDGF in mediating proliferative and other inflammatory events in the glomerulus remains to be identified.
Insights
Human glomerular mesangial cells produce a Platelet-Derived Growth Factor (PDGF)-like protein that stimulates cell growth. This finding suggests PDGF may play a role in glomerular inflammation and proliferation.
Area of Science:
- Nephrology
- Cell Biology
- Molecular Biology
Background:
- Platelet-Derived Growth Factor (PDGF) is a mitogen for mesenchymal cells.
- PDGF is released by platelets, macrophages, endothelial cells, and mesangial cells.
- Glomerular inflammation involves various cell types and growth factors.
Purpose of the Study:
- To investigate the production and function of PDGF-like proteins by human glomerular mesangial cells.
- To determine if human mesangial cells express PDGF mRNA.
- To assess the effect of PDGF on mesangial cell proliferation.
Main Methods:
- Cultured human glomerular mesangial cells.
- Analysis of conditioned medium for PDGF-like activity using 125I-PDGF binding assays and fibroblast mitogenesis assays.
- Use of anti-PDGF antibody to assess cross-reactivity.
- Northern blot analysis to detect PDGF A- and B-chain mRNAs.
- Assessment of PDGF binding to mesangial cells and its effect on DNA synthesis and proliferation.
Main Results:
- Human glomerular mesangial cells in culture release a PDGF-like protein with competing and mitogenic activities.
- This protein is partially recognized by an anti-PDGF antibody.
- Mesangial cells express both PDGF A- and B-chain mRNAs.
- PDGF specifically binds to mesangial cells and stimulates their DNA synthesis and proliferation.
Conclusions:
- Human mesangial cells produce and respond to PDGF-like proteins.
- Secreted PDGF-like proteins may act as autocrine or paracrine growth factors for mesangial cells.
- PDGF may contribute to proliferative and inflammatory processes in the glomerulus, although its precise biological role requires further investigation.