Neutralizing TGF-β1 antibody infusion in neonatal rat delays in vivo glomerular capillary formation1

Neutralizing TGF-β1 antibody infusion in neonatal rat delays in vivo glomerular capillary formation. Background The interruption of transforming growth factor-β (TGF-β) signaling with dominant negative type II TGF-β receptors in bovine glomerular endothelial cells abrogates capillary morphogenesis in vitro , and genetic defects in the TGF-β1 signaling cascade in mice and humans result in abnormalities of blood vessel morphology. This study sought to determine whether TGF-β1 participates in renal glomerular capillary development in vivo. Methods To inhibit TGF-β1 action, neutralizing anti–TGF-β1 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. Results The infusion of neutralizing the TGF-β1 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-β1 antibody. Seven days after TGF-β1 antibody infusion, glomeruli appeared normal, and no reduction in glomerular number was observed. Conclusions These findings suggest that TGF-β1 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-β1.