Localization of extracellular matrix receptors in ICGN mice, a strain of mice with hereditary nephrotic syndrome.
Fibrotic degeneration was examined in the kidneys of ICR-derived glomerulonephritis (ICGN) mice, a novel inbred mouse line with a hereditary nephrotic syndrome of unknown etiology considered to be a good model of human idiopathic nephrotic syndrome. In the present study, we histochemically revealed changes in accumulation of extracellular matrix (ECM) components and in localization of integrins, cellular receptors for ECM, in the kidneys of ICGN mice with the progression of renal failure. Excessive accumulation of basement membrane (laminin and collagen IV) and interstitial (type III collagen) ECM components were demonstrated in the glomeruli and tubulointerstitum of ICGN mice. Marked deposition of type I collagen and tenascin was seen only in the glomeruli of ICGN mice but not in those of ICR mice as normal controls. Increased expression of integrin alpha1-, alpha2-, alpha5- and beta1-subunits in glomeruli with fibrotic degeneration and abnormal distribution of alpha6-subunit were noted in the kidneys of ICGN mice. Excessive laminin, a ligand of alpha6beta1-integrin, was demonstrated on the tubular basement membrane, but alpha6-subunit diffusely disappeared on the basal side of the tubular epithelial cells. We presumed that abnormal integrin expression in renal tubules causes epithelial cell detachment, and consequently tubular nephropathy, and results in disorder of ECM metabolism causing excessive accumulation of ECM components in the kidneys of ICGN mice.
Uchio-Yamada
K
K
Unit of Anatomy and Cell Biology, Department of Animal Sciences, Kyoto University, Japan.
Manabe
N
N
Yamaguchi
M
M
Akashi
N
N
Goto
Y
Y
Yamamoto
Y
Y
Ogura
A
A
Miyamoto
H
H
D000418:Albumins / Q000378:metabolism; D000818:Animals; D001806:Blood Urea Nitrogen; D003404:Creatinine / Q000097:blood; D005109:Extracellular Matrix / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005260:Female; D005921:Glomerulonephritis / Q000097:blood / Q000378:metabolism*; D007150:Immunohistochemistry; D016023:Integrins / Q000378:metabolism*; D007678:Kidney Glomerulus / Q000378:metabolism*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D013047:Specific Pathogen-Free Organisms
D000418:Albumins; D016326:Extracellular Matrix Proteins; D016023:Integrins; D003404:Creatinine