Changes in Quantitative Profile of Extracellular Matrix Components in the Kidneys of Rats with Adriamycin-induced Nephropathy.

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  • MANABE Noboru
    Unit of Anatomy and Cell Biology, Department of Animal Sciences, Kyoto University
  • KINOSHITA Akiko
    Unit of Anatomy and Cell Biology, Department of Animal Sciences, Kyoto University
  • YAMAGUCHI Misuzu
    Unit of Anatomy and Cell Biology, Department of Animal Sciences, Kyoto University
  • FURUYA Yoshihiro
    Unit of Anatomy and Cell Biology, Department of Animal Sciences, Kyoto University
  • NAGANO Nobuo
    Pharmaceutical Research Laboratory, Kirin Brewery Co., Ltd
  • YAMADA-UCHIO Kozue
    Unit of Anatomy and Cell Biology, Department of Animal Sciences, Kyoto University
  • AKASHI Naotsugu
    Unit of Anatomy and Cell Biology, Department of Animal Sciences, Kyoto University
  • MIYAMOTO-KURAMITSU Keiko
    Unit of Anatomy and Cell Biology, Department of Animal Sciences, Kyoto University
  • MIYAMOTO Hajime
    Unit of Anatomy and Cell Biology, Department of Animal Sciences, Kyoto University

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Extracellular matrix components (ECMs) in histological sections of the kidney cortex from the rats with adriamycin (ADR)-induced nephropathy (5 mg/kg, i.v.) were quantified by an immunohistochemical micromethod. Changes in kidney histopathology and urine and blood biochemistry were investigated. Enlarged kidneys were granular on the surface and pale in color in ADR-treated rats, and these rats had kidneys with glomeruli with expanded mesangial area and with capillary aneurysm. Severe albuminuria, hypoalbuminemia, hypercholesterolemia and disorders in other nephrotic parameters were observed in ADR-treated rats. Type I and IV collagens, fibronectin and laminin contents in the renal cortex of ADR-treated rats at 10 weeks were 329, 317, 263 and 295%, respectively, higher than in each vehicle control, and those at 28 weeks were 1,211, 930, 1,057 and 1,012%, respectively. The glomerular sclerotic abnormalities progressed in a time-dependent manner. Moreover, there was a strong correlation between the ECM levels and serum creatinine and blood urea nitrogen levels. In conclusion, microquantification provided useful information for accurate diagnosis and prognosis of nephrotic lesions and is a good tool to assess the advancement of renal disorders in patients with nephropathy.

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