Experimental focal segmental glomerulosclerosis in mice.
Although a lot of animal models of proteinuria have been established, proposals for the mechanisms of proteinuria are still controversial. In this work, during an 18-day trial, mice injected with a single dose of adriamycin (AD) rapidly showed combined glomerular albuminuria and immunoglobulinuria, progressively elevated levels of nitrite/nitrate in urine, hypercholesterolemia, abnormal renal function, segmentally or globally glomerular hyalinosis/sclerosis associated with tubular atrophy, enhanced glomerular deposition of immunoglobulins and fibrinogen, augmented expression of matrix components in the whole glomerular tuft, and loss of glomerular negative charge property. These laboratory and pathological features are comparatively similar to those of human focal segmental glomerulosclerosis in the advanced state. Juxtamedullary glomeruli appear to be more susceptible to the AD-related nephrotoxicity than those in the superficial renal cortex. A change in size-dependent glomerular permselectivity may precede a charge-dependent defect in glomeruli in this mouse model of proteinuria. Data in this study confirm the hypothesis of glomerular hyperfiltration involved in the pathogenesis of this chronic glomerulopathy associated with proteinuria in mice. In addition, nitric oxide may play a crucial role in the progression of the chronic glomerulopathy model.
Chen
A
A
Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC.
Sheu
L F
LF
Ho
Y S
YS
Lin
Y F
YF
Chou
W Y
WY
Chou
T C
TC
Lee
W H
WH
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity; D002784:Cholesterol / Q000097:blood; D004195:Disease Models, Animal; D018450:Disease Progression; D004317:Doxorubicin / Q000633:toxicity; D005260:Female; D005923:Glomerulosclerosis, Focal Segmental / Q000097:blood / Q000139:chemically induced / Q000652:urine; D006417:Hematuria / Q000097:blood; D007150:Immunohistochemistry; D007668:Kidney / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009566:Nitrates / Q000652:urine; D009573:Nitrites / Q000652:urine; D011507:Proteinuria / Q000652:urine; D012709:Serum Albumin / Q000378:metabolism
D000903:Antibiotics, Antineoplastic; D009566:Nitrates; D009573:Nitrites; D012709:Serum Albumin; D004317:Doxorubicin; D002784:Cholesterol