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Modulation of mesangial cell migration by extracellular matrix components. Inhibition by heparinlike
J M Person1, D H Lovett, G J Raugi
1Department of Medicine, University of Washington, Seattle.
Abstract:
Extension of mesangial cells (MC) into the pericapillary space is a pathologic response seen in several forms of glomerulonephritis. This process may involve both cytoplasmic extension by MC and actual cellular migration. For investigation of whether extracellular matrix factors could modulate this process, the migratory responses of rat MC were quantitatively examined using a cell culture model. Denuding ("wounding") a portion of a confluent culture of MC was followed by migration of mesangial cells into the denuded area. The expected proliferative response to this treatment was blocked by irradiation. The migratory response began within 8 hours of wounding and continued for at least 80 hours. The MC migratory response was specifically inhibited in a dose-dependent and reversible manner by heparin and heparinlike glycosaminoglycans (GAGs). Chondroitin sulfates and hyaluronic acid did not significantly inhibit MC migration. Glomerular basement membrane heparinlike GAGs may normally prevent MC extension into the pericapillary space. Changes in the density or composition of these substances during glomerular inflammatory processes could permit the development of MC pericapillary extensions and thereby lead to further alterations in basement membrane integrity.
Insights
Heparin and similar substances inhibit mesangial cell (MC) migration, a key process in glomerulonephritis. This suggests these extracellular matrix factors normally prevent MC extension into the pericapillary space.
Area of Science:
- Nephrology
- Cell Biology
- Extracellular Matrix Biology
Background:
- Mesangial cell (MC) extension into the pericapillary space is a hallmark of glomerulonephritis.
- This pathological process involves MC cytoplasmic extension and cellular migration.
- Extracellular matrix (ECM) factors may influence MC migration.
Purpose of the Study:
- To investigate the role of ECM factors in modulating mesangial cell migration.
- To quantitatively assess the migratory responses of rat MC in a cell culture model.
Main Methods:
- A cell culture model of rat mesangial cells was utilized.
- Confluent MC cultures were wounded to induce migration.
- Proliferation was inhibited by irradiation to isolate migratory responses.
- Inhibition by heparin and glycosaminoglycans (GAGs) was dose-dependent and reversible.
Main Results:
- MC migration into the wounded area began within 8 hours and continued for over 80 hours.
- Heparin and heparinlike GAGs significantly inhibited MC migration in a dose-dependent and reversible manner.
- Chondroitin sulfates and hyaluronic acid did not show significant inhibitory effects on MC migration.
Conclusions:
- Heparinlike GAGs in the glomerular basement membrane may normally restrict MC extension.
- Altered GAGs during glomerular inflammation could facilitate MC pericapillary extensions.
- MC extension may contribute to further damage in basement membrane integrity.