Floege J, Johnson R J, Alpers C E, Fatemi-Nainie S, Richardson C A, Gordon K, Couser W G
Department of Medicine, University of Washington, Seattle 98195.
Am J Pathol. 1993 Feb;142(2):637-50.
In glomerular diseases associated with antibody- and complement-mediated injury to endothelial and mesangial cells, cell proliferation is an important early response that precedes matrix accumulation and glomerulosclerosis. In contrast, in diseases in which the visceral glomerular epithelial cell (vGEC) is the principal target of injury, cell proliferation is not a recognized consequence, although vGECs respond in vitro to a variety of growth factors and inflammatory mediators. To explore the possibility that low levels of vGEC proliferation may occur and participate in such diseases, serial studies were done in the passive Heymann nephritis model of membranous nephropathy, in which the vGEC is the primary target of antibody- and C5b-9-mediated injury. The results showed mitotic figures and positive staining for the proliferating cell nuclear antigen in cells whose location defined them as vGECs. The proliferating cell nuclear antigen-positive cells at the edge of the capillary wall were confirmed to be vGECs by double-immunostaining with antibodies to SPARC/osteonectin, which preferentially label vGECs in passive Heymann nephritis. Proliferation of vGECs in vivo was preceded by increased glomerular expression of platelet-derived growth factor (PDGF) B-chain protein and messenger RNA, both of which localized to vGECs. PDGF B-chain protein and messenger RNA were also detected in cultured vGECs. PDGF receptor beta-subunit protein or messenger RNA could not be demonstrated in vGECs in vivo or in vitro, and no growth response of cultured vGECs to PDGF was noted. These results suggest that proliferation of vGECs does occur in a model of glomerular injury induced by antibody and C5b-9 on vGECs. VGEC proliferation and production of PDGF may be involved in the restoration of the capillary wall but could also contribute to local capillary wall injury and proliferation of other cells in Bowman's capsule, interstitium, and tubules.
在与抗体和补体介导的内皮细胞及系膜细胞损伤相关的肾小球疾病中，细胞增殖是基质积聚和肾小球硬化之前的重要早期反应。相比之下，在内脏肾小球上皮细胞（vGEC）是主要损伤靶点的疾病中，尽管vGECs在体外对多种生长因子和炎症介质有反应，但细胞增殖并非公认的结果。为了探究vGEC低水平增殖可能发生并参与此类疾病的可能性，我们在膜性肾病的被动海曼肾炎模型中进行了系列研究，在该模型中vGEC是抗体和C5b - 9介导损伤的主要靶点。结果显示，在位置确定为vGECs的细胞中出现有丝分裂象以及增殖细胞核抗原的阳性染色。通过用SPARC/骨连接蛋白抗体进行双重免疫染色，证实毛细血管壁边缘的增殖细胞核抗原阳性细胞为vGECs，该抗体在被动海曼肾炎中优先标记vGECs。vGECs在体内增殖之前，肾小球中血小板衍生生长因子（PDGF）B链蛋白和信使核糖核酸的表达增加，二者均定位于vGECs。在培养的vGECs中也检测到了PDGF B链蛋白和信使核糖核酸。在vGECs体内或体外均未证实有PDGF受体β亚基蛋白或信使核糖核酸，并且未观察到培养的vGECs对PDGF有生长反应。这些结果表明，在由抗体和C5b - 9诱导的vGECs肾小球损伤模型中确实发生了vGECs增殖。vGECs增殖和PDGF的产生可能参与毛细血管壁的修复，但也可能导致局部毛细血管壁损伤以及鲍曼囊、间质和肾小管中其他细胞的增殖。
