Endothelial Cell Apoptosis during Glomerular Capillary Lumen Formation In Vivo

Publisher Website
Google Scholar
Abstract
Transforming growth factor–β (TGF-β) stimulates endothelial cell apoptosis in vitro, and inhibition of TGF-β1 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-β1–dependent endothelial cell apoptosis. Neutralizing anti-TGF-β1 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-β1 antibody or control IgY, the frequency of endocapillary apoptotic cells was 0.03 and 0.09/loop, respectively (P < 0.001, χ2). 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. E-mail: bjballer@aecom.yu.edu