Participation of glomerular endothelial cells in the capillary repair of glomerulonephritis.
Participation of glomerular endothelial cells in the capillary repair of glomerulonephritis.
复制标题
DOI：
--
复制
发表时间：
1995-12
期刊：
影响因子：
--
通讯作者：
L. Iruela-Arispe;K. Gordon;C. Hugo;A. Duijvestijn;K. Claffey;M. Reilly;W. Couser;C. Alpers;Richard J. Johnson
中科院分区：
文献类型：
--
作者：
L. Iruela-Arispe;K. Gordon;C. Hugo;A. Duijvestijn;K. Claffey;M. Reilly;W. Couser;C. Alpers;Richard J. Johnson
在许多肾小球疾病中，可能会发生严重的系膜损伤，导致基质溶解和肾小球毛细血管受损。虽然肾小球结构的破坏可能导致永久性损伤，但在某些情况下会自动恢复。调解这一复苏的机制尚不清楚。在这项研究中，我们提供了成人肾小球损伤后肾小球毛细血管修复(血管生成)的证据。向大鼠体内注射抗Thy-1抗体可导致严重的系膜溶解，毛细血管充盈、微动脉瘤形成，除系膜细胞外，还可见内皮细胞丢失。虽然系膜细胞增殖是损伤的主要反应，但与毛细血管修复相关的内皮细胞增殖也可在第2至14天被记录下来。内皮细胞的增殖在第2天和第7天达到高峰，此时内皮细胞的增殖是正常的7到9倍。许多内皮细胞表现出血管生成的形态特征。使用中和抗碱性成纤维细胞生长因子抗体(P<；0.001)，内皮细胞增殖的初始波可以减少40%。晚期肾小球内皮细胞的增殖与血管通透性因子/血管内皮细胞生长因子(VPF/VEGF)的表达上调和VPF/VEGF受体Flk的增加有关。尽管PDGF在该模型中表达，但抗PDGF抗体处理不影响内皮细胞的增殖反应。综上所述，肾小球内皮细胞在肾小球损伤反应中起着积极作用。肾小球能够修复微动脉瘤，其机制涉及碱性成纤维细胞生长因子和血管内皮生长因子/血管内皮生长因子介导的内皮细胞增殖反应。
In many glomerular diseases severe injury to the mesangium may occur, leading to matrix dissolution and damage to the glomerular capillaries. Although the destruction of glomerular architecture may lead to permanent injury, in some cases spontaneous recovery occurs. The mechanisms that mediate this recovery are unknown. In this study we provide evidence for glomerular capillary repair (angiogenesis) in the adult injured glomerulus. Injection of anti-Thy 1 antibody into rats results in severe mesangiolysis with capillary ballooning, microaneurysm formation, and loss of endothelial cells in addition to mesangial cells. Although mesangial proliferation is a major response to injury, proliferation of endothelial cells also can be documented from days 2 to 14 in association with repair of the capillaries. The endothelial cell proliferation peaks on days 2 and 7, when it is seven- to ninefold greater than normal. Many of the endothelial cells display morphological features of angiogenesis. The initial wave of endothelial cell proliferation can be reduced by 40% with neutralizing anti-basic fibroblast growth factor antibodies (P < 0.001). The later glomerular endothelial cell proliferation is associated with upregulated expression of vascular permeability factor/endothelial cell growth factor (VPF/VEGF) and an increase of flk, a VPF/VEGF receptor. Although PDGF is expressed in this model, anti-PDGF antibody treatment did not affect the endothelial cell proliferative response. In summary, glomerular endothelial cells have an active role in the glomerular response to injury. Glomeruli are capable of healing microaneurysms, and the mechanism involves basic fibroblast growth factor- and VPF/VEGF-mediated endothelial proliferative responses.