Dissociation of mesangial cell migration and proliferation in experimental glomerulonephritis
Dissociation of mesangial cell migration and proliferation in experimental glomerulonephritis
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DOI：
10.1046/j.1523-1755.1999.00641.x
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发表时间：
1999-09-01
影响因子：
19.6
通讯作者：
Johnson, RJ
中科院分区：
文献类型：
--
作者：
Haseley, LA;Hugo, C;Johnson, RJ
背景最近，我们记录了Thy 1模型中的体内系膜细胞（MC）消融后，系膜的重建发生在Thy 1（OX-7）阳性细胞从门和肾小球外系膜的协调增殖和迁移。我们研究了碱性成纤维细胞生长因子（bFGF）在这些事件的调解中的作用。给大鼠注射抗胸腺细胞血清，48小时后用H-3-胸苷脉冲标记增殖细胞。90分钟后，获得基线肾活检，并向大鼠注射中和抗bFGF抗体或对照IgG。在发病96小时时进行牺牲活检。使用计算机图像分析，定量两个时间点的活检组织中放射性标记MC（增殖）的数量及其与肺门的平均距离（迁移）。采用趋化实验检测bFGF对MCs迁移的影响。在处死时，与接受对照IgG的大鼠相比，接受抗bFGF的大鼠的放射自显影具有显著更少的放射性标记的MC（5.7 +/- 1.9 vs. 14.7 +/- 3.5，P = 0.0001），产生总体40%的增殖减少。然而，两组中放射性标记的MC与肾小球门的最终距离无差异，表明在该模型中给予抗bFGF并不影响MC迁移。在体外趋化试验中，MCs对血小板衍生生长因子（PDGF）BE（20 ng/ml）有迁移反应，但对bFGF在较宽浓度范围（0.5 - 50 ng/ml）无迁移反应。这些研究表明，碱性成纤维细胞生长因子是MC增殖的重要介质，但它并不显着影响MC迁移。这是第一次证明影响增殖的介质可以与介导肾损伤迁移的介质分离。
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 originating from the hilus and extraglomerular mesangium. We investigated the role of basic fibroblast growth factor (bFGF) in the mediation of these events.Methods. Rats were injected with antithymocyte serum and 48 hours later were pulsed with H-3-thymidine to label proliferating cells. Ninety minutes later, a baseline renal biopsy was obtained, and rats were injected with neutralizing anti-bFGF antibodies or control IgG. Sacrificial biopsies were obtained at 96 hours of disease. Using computer image analysis, biopsies from both time points were quantitated for the number of radiolabeled MC (proliferation) and their mean distance from the hilus (migration). The effect of bFGF on the migration of MCs in culture was examined using a chemotactic assay.Results. At sacrifice, autoradiographs of rats receiving anti-bFGF had significantly fewer radiolabeled MCs as compared with rats receiving control IgG (5.7 +/- 1.9 vs. 14.7 +/- 3.5, P = 0.0001), yielding an overall 40% reduction in proliferation. There was no difference, however, in the final distance of radiolabeled MCs from the glomerular hilus in the two groups, indicating that the administration of anti-bFGF did not effect MC migration in this model. In an in vitro chemotactic assay, MCs migrated in response to platelet-derived growth factor (PDGF) BE (20 ng/ml), but did not migrate in response to bFGF at a wide range of concentrations (0.5 to 50 ng/ml).Conclusions. These studies demonstrate that bFGF is an important mediator of MC proliferation but that it does not significantly influence MC migration. This is the first demonstration showing that the mediators effecting proliferation can be dissociated from those mediating migration in renal injury.