Dissociation of mesangial cell migration and proliferation in experimentalglomerulonephritis

Background. Recently, we documented that following in vivo mesangial cell ( MC) ablation in the Thy1 model, reconstitution of the mesangium occurs by a coordinated proliferation and migration of Thy1 (OX-7)-positive cells orig inating from the hilus and extraglomerular mesangium. We investigated the r ole of basic fibroblast growth factor (bFGF) in the mediation of these even ts. Methods. Rats were injected with antithymocyte serum and 48 hours later wer e pulsed with H-3-thymidine to label proliferating cells. Ninety minutes la ter, a baseline renal biopsy was obtained, and rats were injected with neut ralizing anti-bFGF antibodies or control IgG. Sacrificial biopsies were obt ained at 96 hours of disease. Using computer image analysis, biopsies from both time points were quantitated for the number of radiolabeled MC (prolif eration) and their mean distance from the hilus (migration). The effect of bFGF on the migration of MCs in culture was examined using a chemotactic as say. Results. At sacrifice, autoradiographs of rats receiving anti-bFGF had sign ificantly fewer radiolabeled MCs as compared with rats receiving control Ig G (5.7 +/- 1.9 vs. 14.7 +/- 3.5, P = 0.0001), yielding an overall 40% reduc tion in proliferation. There was no difference, however, in the final dista nce of radiolabeled MCs from the glomerular hilus in the two groups, indica ting that the administration of anti-bFGF did not effect MC migration in th is model. In an in vitro chemotactic assay, MCs migrated in response to pla telet-derived growth factor (PDGF) BE (20 ng/ml), but did not migrate in re sponse to bFGF at a wide range of concentrations (0.5 to 50 ng/ml). Conclusions. These studies demonstrate that bFGF is an important mediator o f MC proliferation but that it does not significantly influence MC migratio n. This is the first demonstration showing that the mediators effecting pro liferation can be dissociated from those mediating migration in renal injur y.