| Co-Investigator(Kenkyū-buntansha) |
YAO Jian Faculty OF MEDICINE, Dept. Cellular Physiology, Niigata University, Assistant, 医学部, 助手 (50303128)
OITE Takashi Faculty OF MEDICINE, Dept. Cellular Physiology, Niigata University, Professor, 医学部, 教授 (60018744)
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| Research Abstract |
Angiogenesis has been demonstrated to play a pivotal role in regeneration of glomerular structure in the reversible model of glomerulonephritis. But it remains unknown whether impairment of vascular generation leads to progressive glomerulosclerosis. In the Present project, we have developed the irreversible glomerulosclerosis model and examine the role of glomerular endothelial cell responses in the process of progressive sclerotic changes. Rats were injected with anti-Thy1 monoclonal antibody, 1-22-3, and then 30 minutes after injection, unilateral nephrectomy (Nx) or sham operation (sham) was performed. Rats were sacrificed on day 3, 14, 56 and 84 after infection, and light microscopic examination was performed. The glomerular capillary density was estimated by immunofluorescence staining for anti-CD31(PECAM-1) and anti-rat endothelial cell antigens(RECA-1) antibody. We also examined the glomerular mRNA expressions for PECAM-1 and vascular cell adhesion molecule-1 (VCAM-1) as endothelial cell markers, and vascular endothelial cell growth factor (VEGF) as an angiogenic factor using semi-quantitative RT-PCR. Mesangiolytic changes on day 3 and diffuse mesangial cell proliferation on day 14 were found in the same degree in both Nx and sham, but the capillary density was significantly lower in Nx on day 14. In addition, expressions of mRNAs for PECAM-1, VCAM-1 and VEGF were significantly lower in Nx than sham on day 14. Although mesangial cell proliferation was decreased and the capillary density was recovered on day 56, progressive glomerular lesion with tubulointerstitial changes found sclerotic changes were occurred together with the decrease of the capillary density in Nx on day 84, while glomerular structure was almost normal in sham.
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