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Kidney Int. 2002 Feb;61(2):432-43.

Impairment of vascular regeneration precedes progressive glomerulosclerosis in anti-Thy 1 glomerulonephritis.

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1
Department of Cellular Physiology, Institute of Nephrology, Niigata University School of Medicine, and Gosen Jin-Ai Clinic, Niigata, Japan.

Abstract

BACKGROUND:

It has been proposed that glomerular hemodynamic changes or glomerular growth response may promote the development of glomerulosclerosis, irrespective of its etiology. Further experimental models are needed to clarify the cellular and molecular mechanisms that lead to progressive glomerulosclerosis with an irreversible course. We designed a model of irreversible glomerulosclerosis, using anti-Thy-1.1 injection followed by uninephrectomy, and examined the role of glomerular endothelial cell responses in the process of progressive sclerotic changes.

METHOD:

Rats were injected with anti-Thy-1.1 monoclonal antibody, 1-22-3, and 30 minutes later, unilateral nephrectomy (one-kidney group) or sham operation (two-kidney group) was performed. Rats were sacrificed for histological examination on days 3, 14, 56, and 84 after injection. The density of the glomerular capillary tuft was assessed by immunofluorescent staining for endothelial specific antigens. The mRNA expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), platelet-endothelial cell adhesion molecule-1 (PECAM-1), and vascular endothelial growth factor (VEGF) also was followed up by reverse transcription-polymerase chain reaction (RT-PCR).

RESULTS:

Semiquantitative analysis revealed that the capillary density and mRNA expression of PECAM-1, VCAM-1 and VEGF were significantly lower in the one-kidney group compared to the two-kidney group on day 14. On day 84, progressive glomerulosclerotic lesions were found, followed by a decrease of the capillary density in the one-kidney group, while the glomerular architecture recovered to an almost normal state in the two-kidney group.

CONCLUSIONS:

Progressive glomerulosclerosis can be induced in the rat by a one shot injection of anti-Thy 1.1 monoclonal antibody followed by unilateral nephrectomy. This model shows that there is a positive association between impairment of vascular regeneration and the development of glomerulosclerosis.

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