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Published on: November 1, 2007
Production of platelet-derived growth factorlike protein by rat mesangial cells in culture
Abstract:
Rat mesangial cells (MC) release a factor that competes in a dose-dependent manner with 125I-labeled platelet-derived growth factor (PDGF) for binding to human foreskin fibroblasts (HFF). The competitor activity in mesangial cell conditioned medium (MCCM) is reversible, trypsin sensitive, and inhibited by anti-PDGF IgG. MCCM also expresses potent mitogenic activity to HFF. Anti-PDGF IgG, in concentrations that completely abolished the mitogenic activity of pure PDGF and the competitor activity of MCCM, only partially (33-41%) inhibits this mitogenic activity. The PDGF receptor competing activity as well as the total mitogenic activity, coelutes with labeled pure PDGF on Sephacryl S-200 gel chromatography. Cation exchange chromatography of concentrated MCCM yields a major mitogen peak with little competitor activity and a smaller mitogenic peak with comparable competitor activity, suggestive of the presence of other mitogens in MCCM besides the PDGF-like protein. PDGF is a potent mitogen and may play a role at inflammatory sites. The production of PDGF-like protein by MC may provide insights for understanding the pathogenesis of glomerular diseases.
Insights
Rat mesangial cells release a platelet-derived growth factor (PDGF)-like protein that competes with PDGF binding. This protein, along with other mitogens, may contribute to glomerular disease pathogenesis.
Area of Science:
- Cell Biology
- Molecular Biology
- Nephrology
Background:
- Platelet-derived growth factor (PDGF) is a potent mitogen involved in inflammatory processes.
- Mesangial cells (MC) are key components of the glomerulus and play a role in kidney diseases.
Purpose of the Study:
- To investigate the presence and characteristics of PDGF-like factors released by rat mesangial cells.
- To explore the role of these factors in mesangial cell-mediated mitogenic activity.
Main Methods:
- Characterization of conditioned medium from mesangial cells (MCCM) using binding assays with 125I-labeled PDGF.
- Enzyme treatments (trypsin) and antibody inhibition (anti-PDGF IgG) were employed.
- Gel chromatography (Sephacryl S-200) and cation exchange chromatography were used for purification and analysis.
Main Results:
- MCCM contains a factor that competes with PDGF binding to human foreskin fibroblasts (HFF) in a dose-dependent manner.
- This competitor activity is reversible, trypsin-sensitive, and inhibited by anti-PDGF IgG.
- MCCM exhibits mitogenic activity on HFF, partially inhibited by anti-PDGF IgG, suggesting the presence of other mitogens besides the PDGF-like protein.
Conclusions:
- Rat mesangial cells produce a PDGF-like protein with receptor-binding competitor activity.
- MCCM contains both PDGF-like protein and other mitogenic factors.
- The production of PDGF-like protein by MC may offer insights into the pathogenesis of glomerular diseases.
