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(American Journal of Pathology. 2002;161:135-143.)
© 2002 American Society for Investigative Pathology

Regular Articles

Blockade of Platelet-Derived Growth Factor Receptor-ß Pathway Induces Apoptosis of Vascular Endothelial Cells and Disrupts Glomerular Capillary Formation in Neonatal Mice

Hideto Sano^*, Yukihiko Ueda^*¶, Nobuyuki Takakura, Genzou Takemura, Toshio Doi, Hiroshi Kataoka^*, Toshinori Murayama^*, Yang Xu^*, Tetsuo Sudo, Satomi Nishikawa, Shin-Ichi Nishikawa, Hisayoshi Fujiwara, Toru Kita^* and Masayuki Yokode^*

From the Departments of Geriatric Medicine^*and Molecular Genetics,Graduate School of Medicine, Kyoto University, Kyoto; the Second Department of Internal Medicine,Gifu University School of Medicine, Gifu; and the Department of Laboratory Medicine,School of Medicine, The University of Tokushima, Tokushima,^¶Shiga Medical Center Research Institute, Japan

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- and PDGFR-ß, have been identified and we previously analyzed the effects of blockade of PDGFR- signal in neonatal mice. In the current study, we examined the role of PDGFR-ß in glomerular development by blocking PDGFR-ß signal in neonatal mice by administration of antagonistic anti-PDGFR-ß monoclonal antibody. Unlike the mice injected with anti-PDGFR- antibody, the mice injected daily with anti-PDGFR-ß 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-ß is not expressed in the endothelial cells, the effects of the blockade of PDGFR-ß might have caused glomerular endothelial cell apoptosis by inducing the loss of mesangial cells and/or pericytes.

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