Time course study of the extracellular matrix in puromycin-aminonucleoside-induced glomerulosclerosis.

Abstract

The purpose of this study was to investigate the mechanism of glomerulosclerosis, which is an important histopathological feature of various renal diseases. Puromycin aminonucleoside (PAN) was administered to rats to produce glomerular lesions, and the kidneys were examined by repeated renal biopsy with light microscopy and immunohistochemical detection of glomerular extracellular matrix (ECM) components (laminin, fibronectin, type I, III, and IV collagen). Immunohistochemical studies utilizing the streptavidin-biotin method showed marked accumulation of laminin and type IV collagen in the adhesions between the glomerular epithelium and Bowman's capsule, as well as in the mesangial matrix. Fibronectin was detected in the normal mesangium and the basement membrane of Bowman's capsule, while adhesions and the matrix accumulations were also positive. The sclerotic lesions of the glomeruli were also stained for type I and III collagen, which exist in normal interstitial tissue, but never in healthy glomeruli. Type I collagen appeared in the lesions after type III collagen. All of the ECM components examined in this study were present in advanced glomerulosclerosis and showed distinctive patterns of progression. These finding suggest that abnormal accumulation and production of ECM components in the glomeruli may have a role in the development of glomerulosclerosis.