Localization of tissue transglutaminase (tTG) in kidney of ICR-derived glomerulonephritis (ICGN) mice.
ICR-derived glomerulonephritis (ICGN) mice are a known inbred strain with hereditary nephrotic syndrome and are considered a good animal model of human idiopathic nephrotic syndrome. ICGN mice show proteinuria at a young age, and hypoalbuminemia, hyperlipidemia, anemia and edema accompanies their symptoms with aging. In addition, ICGN mice develop severe anemia with the progression of renal fibrosis similar to human chronic kidney disease (CKD). Recently, tissue transglutaminase (tTG) has been shown to be related to the renal fibrosis in several animal models and CKD patients. In the present study, we investigated the relationship between the progression of renal fibrosis and the localization of tTG in the kidneys using histochemistry and image analysis. Male ICGN mice aged 26-43 weeks were used. They were divided into two groups of early and terminal stages of renal fibrosis, based on plasma levels of blood urea nitrogen (BUN). Normal ICR males aged 11 weeks were used as a control group. tTG was localized to the interstitium in the normal ICR mice. In the early stage of renal fibrosis, the localization of tTG increased in renal tubules showing luminal dilation, as well as in the interstitium; however, the amount of tubular and interstitial tTG decreased in the late stage. In the glomeruli, tTG-immunoreactivity decreased in the late stage of renal fibrosis, despite the progression of glomerular sclerosis. The results suggest that epsilon(gamma-glutamyl) lysine cross-linking is not directly related to the progression of renal fibrosis in ICGN mice.
Miyamoto
Yohei
Y
Toxicology and Pharmacokinetics Laboratories, Pharmaceutical Research Laboratories, Toray Industries, Inc, Tebiro, Kamakura, Kanagawa, Japan.
Myomoto
Akira
A
Sakaguchi
Yuka
Y
Yamaguchi-Yamada
Misuzu
M
Uchio-Yamda
Kozue
K
Manabe
Noboru
N
D000818:Animals; D001806:Blood Urea Nitrogen; D001835:Body Weight; D003404:Creatinine / Q000097:blood; D004195:Disease Models, Animal; D005109:Extracellular Matrix / Q000201:enzymology / Q000473:pathology; D005355:Fibrosis / Q000201:enzymology / Q000473:pathology; D005921:Glomerulonephritis / Q000201:enzymology* / Q000473:pathology; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry / Q000379:methods; D007668:Kidney / Q000201:enzymology* / Q000473:pathology; D007678:Kidney Glomerulus / Q000201:enzymology / Q000473:pathology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009929:Organ Size; D011503:Transglutaminases / Q000378:metabolism*
D003404:Creatinine; D011503:Transglutaminases