Endothelial cell apoptosis during glomerular capillary lumen formation in vivo
Endothelial cell apoptosis during glomerular capillary lumen formation in vivo
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DOI：
10.1097/01.asn.0000061779.70530.06
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发表时间：
2003-05-01
影响因子：
13.6
通讯作者：
Ballermann, BJ
中科院分区：
文献类型：
--
作者：
Fierlbeck, W;Liu, AL;Ballermann, BJ
转化生长因子-β（TGF-β）在体外刺激内皮细胞凋亡，并且TGF-β 1的抑制导致未分化的内皮细胞保留在发育中的肾小球毛细血管中并减少体内管腔形成。本研究探讨了体内肾小球毛细血管腔形成是否涉及TGF-β 1依赖的内皮细胞凋亡的问题。将中和性抗TGF-β 1或非免疫IgY注入3d龄大鼠的肾动脉，2d后检查肾脏。通过透射电镜观察，毛细血管内凋亡细胞的频率为0.10/环在未成熟的肾小球的3-D-岁的大鼠幼崽。在5日龄的大鼠中，给予中和TGF-β 1抗体或对照IgY，毛细血管内凋亡细胞的频率分别为0.03和0.09个/袢（P < 0.001，χ（2））。TUNEL和抗血管性血友病因子（vWF）抗体的双重标记表明，5日龄大鼠幼仔未成熟肾小球中的凋亡细胞是内皮细胞。定量分析显示，与对照组相比，抗TGF-β1抗体输注后肾小球中TUNEL/vWF标记的细胞显著减少。在C形或S形小体中，在任何组中均未观察到毛细血管内凋亡细胞，并且TUNEL分析显示在成熟大鼠的肾脏中未观察到肾小球凋亡细胞。这些发现表明，多余的内皮细胞通过凋亡从未成熟的肾小球毛细血管中清除，这是一个受TGF-β1调节的过程。结合先前的发现，即TGF-β1阻断在体内使肾小球毛细血管腔形成变钝，提出TGF-β1依赖性细胞凋亡在肾小球发育期间用于打开该血管床中的毛细血管腔。
Transforming growth factor-beta (TGF-beta) stimulates endothelial cell apoptosis in vitro, and inhibition of TGF-beta1 leads to retention of undifferentiated endothelial cells in developing glomerular capillaries and reduced lumen formation in vivo. This study explored the question whether glomerular capillary lumen formation in vivo may involve TGF-beta1-dependent endothelial cell apoptosis. Neutralizing anti-TGF-beta1 or non-immune IgY were infused into the renal arteries of 3-d-old rats, and the kidneys were examined 2 d later. By transmission electron microscopy, endocapillary apoptotic cells were observed at a frequency of 0.10/loop in immature glomeruli of 3-d-old rat pups. In 5-d-old rat pups given neutralizing TGF-beta1 antibody or control IgY, the frequency of endocapillary apoptotic cells was 0.03 and 0.09/loop, respectively (P < 0.001, χ(2)). Dual labeling with TUNEL and anti-von Willebrand factor (vWF) antibody showed that apoptotic cells in immature glomeruli of 5-d-old rat pups are endothelial cells. Quantitative analysis showed significantly fewer TUNEL/vWF-labeled cells in glomeruli after anti-TGF-β1 antibody infusion than in controls. No endocapillary apoptotic cells were observed in any group in C-shaped or S-shaped bodies, and the TUNEL assay revealed no glomerular apoptotic cells in kidneys from mature rats. These findings suggest that superfluous endothelial cells are cleared from immature glomerular capillaries by apoptosis, a process regulated by TGF-β1. Taken together with the previous finding, that TGF-β1 blockade blunts glomerular capillary lumen formation in vivo, it is proposed that TGF-β1-dependent apoptosis serves to open capillary lumens in this vascular bed during glomerular development.