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Mesangial cell migration precedes proliferation in Habu snake venom-induced glomerular injury
J L Barnes1, K A Hevey, R R Hastings
1Department of Medicine, University of Texas Health Science Center, San Antonio.
Background:
Mesangial cells migrate in response to platelet released products in vitro (Am J Pathol 1991;138:859). Cell migration, in addition to proliferation might play a role in cell remodeling during the course of proliferative glomerular disease.
Experimental Design:
In this study, we examined mesangial cell migration in vivo in a platelet-dependent model of proliferative glomerulonephritis induced by Habu snake venom. Mesangial cell migration was assessed by phenotypic identification and temporal location of mesangial cells within glomerular lesions in serial time studies from 8 to 48 hours after Habu snake venom. Autoradiography of [3H]thymidine incorporation into cells was employed to identify and temporally separate cell division and proliferation from cell motility and other related events.
Results:
Early (8-hour) lesions consisted of microaneurysms devoid of mesangial cells. By 24 hours, glomeruli showed mesangial cells at the margins of lesions adjacent to intact glomerular tufts, followed by the presence of clusters of cells at 30 and 36 hours. By 48 hours, most lesions were filled with proliferating mesangial cells. Cells containing [3H]thymidine were rarely observed until 30 hours, at which point they were found in advanced lesions. Marginating cells did not contain [3H]thymidine, suggesting that the location of these cells was not related to cell division but rather to migration. Platelet depletion eliminated platelets from lesions and substantially retarded mesangial cell migration into glomerular lesions indicating mesangial cell migration is, in part, dependent on platelets or their secretory products.
Conclusions:
These studies show that mesangial cells can migrate in vivo and suggest that cell migration is an important early step in cell redistribution and remodeling during glomerular injury in this model of proliferative glomerulonephritis.
Insights
Mesangial cell migration in vivo is a key early event in proliferative glomerulonephritis, driven partly by platelet activity. This migration precedes cell proliferation in glomerular injury.
Area of Science:
- Nephrology
- Cell Biology
- Pathology
Background:
- Mesangial cell migration is implicated in glomerular remodeling during proliferative glomerulonephritis.
- Platelet products are known to induce mesangial cell migration in vitro.
Purpose of the Study:
- To investigate in vivo mesangial cell migration in a platelet-dependent model of glomerulonephritis.
- To differentiate cell migration from cell proliferation in glomerular injury.
Main Methods:
- Induction of glomerulonephritis using Habu snake venom in a rat model.
- Serial time studies (8-48 hours) assessing mesangial cell location and phenotype.
- Autoradiography with [3H]thymidine to distinguish cell division from migration.
- Platelet depletion to assess platelet dependence of migration.
Main Results:
- Early glomerular lesions (8 hours) lacked mesangial cells.
- Mesangial cells appeared at lesion margins by 24 hours, migrating before significant proliferation (detected by [3H]thymidine incorporation after 30 hours).
- Platelet depletion significantly inhibited mesangial cell migration into glomerular lesions.
Conclusions:
- Mesangial cells exhibit in vivo migration during glomerular injury.
- Cell migration is a crucial early step in mesangial cell redistribution and tissue remodeling in this model of proliferative glomerulonephritis.
- Platelets or their products play a significant role in mediating mesangial cell migration in vivo.