Liu A, Dardik A, Ballermann B J
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Kidney Int. 1999 Oct;56(4):1334-48. doi: 10.1046/j.1523-1755.1999.00661.x.
The interruption of transforming growth factor-beta (TGF-beta) signaling with dominant negative type II TGF-beta receptors in bovine glomerular endothelial cells abrogates capillary morphogenesis in vitro, and genetic defects in the TGF-beta1 signaling cascade in mice and humans result in abnormalities of blood vessel morphology. This study sought to determine whether TGF-beta1 participates in renal glomerular capillary development in vivo.
To inhibit TGF-beta1 action, neutralizing anti-TGF-beta1 IgG was infused intra-arterially into the suprarenal aorta of three-day-old rats, and the glomerular endothelial cell appearance was evaluated two days later by immunohistochemical detection of the endothelium-specific von Willebrand factor, in situ analysis of vascular endothelial growth factor receptor binding, and morphometric study of developing glomerular structures by transmission electron microscopy.
The infusion of neutralizing the TGF-beta1 antibody markedly reduced the invasion of comma- and S-shaped bodies by endothelial cells, and inhibited organization of endothelial cells into capillaries in these structures. In addition, capillary lumen formation and endothelial cell fenestration in developing cortical, but not in deep, already mature glomeruli were inhibited by neutralizing TGF-beta1 antibody. Seven days after TGF-beta1 antibody infusion, glomeruli appeared normal, and no reduction in glomerular number was observed.
These findings suggest that TGF-beta1 plays a critical role in the formation of glomerular capillaries during renal development in the rat, and that flattening and fenestration of glomerular capillaries require the action of TGF-beta1.
在牛肾小球内皮细胞中用显性负性II型转化生长因子-β（TGF-β）受体阻断TGF-β信号传导可消除体外毛细血管形态发生，而小鼠和人类TGF-β1信号级联反应中的基因缺陷会导致血管形态异常。本研究旨在确定TGF-β1是否参与体内肾小球毛细血管发育。
为抑制TGF-β1的作用，将中和性抗TGF-β1 IgG经动脉注入3日龄大鼠的肾上腺主动脉，两天后通过免疫组织化学检测内皮特异性血管性血友病因子、血管内皮生长因子受体结合的原位分析以及透射电子显微镜对发育中的肾小球结构进行形态计量学研究来评估肾小球内皮细胞外观。
注入中和性TGF-β1抗体显著减少了内皮细胞对逗号状和S形小体的侵入，并抑制了这些结构中内皮细胞组织形成毛细血管。此外，中和性TGF-β1抗体抑制了发育中的皮质肾小球（而非深部已成熟的肾小球）的毛细血管腔形成和内皮细胞窗孔形成。注入TGF-β1抗体7天后，肾小球外观正常，未观察到肾小球数量减少。
这些发现表明，TGF-β1在大鼠肾脏发育过程中肾小球毛细血管形成中起关键作用，并且肾小球毛细血管的扁平化和窗孔形成需要TGF-β1的作用。
