Blockade of platelet-derived growth factor receptor-beta pathway induces apoptosis of vascular endothelial cells and disrupts glomerular capillary formation in neonatal mice.
Platelet-derived growth factor (PDGF), a potent chemotactic and proliferation factor for mesenchymal-derived cells, has been demonstrated to play critical roles in kidney development. Two receptors for PDGF, PDGFR-alpha and PDGFR-beta, have been identified and we previously analyzed the effects of blockade of PDGFR-alpha signal in neonatal mice. In the current study, we examined the role of PDGFR-beta in glomerular development by blocking PDGFR-beta signal in neonatal mice by administration of antagonistic anti-PDGFR-beta monoclonal antibody. Unlike the mice injected with anti-PDGFR-alpha antibody, the mice injected daily with anti-PDGFR-beta antibody could be kept alive at least for 2 weeks after birth but showed severe disruption of the glomerular structure, whereas no apparent deformation was observed in the collecting ducts. In the disrupted glomeruli, the number of the mesangial cells was reduced markedly. Electron microscopic analysis and immunohistochemical studies with terminal deoxynucleotidyl transferase nick-end labeling staining revealed that the capillary endothelial cells of the glomeruli in the outer cortex region underwent apoptosis. However, the glomeruli located near the medulla were less affected. Because PDGFR-beta is not expressed in the endothelial cells, the effects of the blockade of PDGFR-beta might have caused glomerular endothelial cell apoptosis by inducing the loss of mesangial cells and/or pericytes.
Sano
Hideto
H
Department of Geriatric Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Ueda
Yukihiko
Y
Takakura
Nobuyuki
N
Takemura
Genzou
G
Doi
Toshio
T
Kataoka
Hiroshi
H
Murayama
Toshinori
T
Xu
Yang
Y
Sudo
Tetsuo
T
Nishikawa
Satomi
S
Nishikawa
Shin-Ichi
S
Fujiwara
Hisayoshi
H
Kita
Toru
T
Yokode
Masayuki
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017209:Apoptosis / Q000502:physiology*; D002196:Capillaries / Q000187:drug effects / Q000254:growth & development*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D005260:Female; D007678:Kidney Glomerulus / Q000098:blood supply* / Q000187:drug effects; D051379:Mice; D008813:Mice, Inbred ICR; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000037:antagonists & inhibitors / Q000276:immunology / Q000502:physiology*
D000911:Antibodies, Monoclonal; D020797:Receptor, Platelet-Derived Growth Factor beta