The Influence of Adriamycin on the Morphologic Alteration and the Expression of Laminin in the Renal Glomerular Basement Membrane of Rat

Chung, Ho Sam; Han, Sang Woong; Kim, Ho Jung

Abstract

Laminin is a glycoprotein that is composed of the basement membrane of renal glomerulus and various tissues, such as epithelium, nervous tissue, and muscle tissues. Functions of laminin have been demonstrated to play an essential role in the regeneration and polarity of cells as well as the reservation of materials inside of the tissues. In collaboration with type IV collagen, heparan sulfate proteoglycan, and fibronectin, laminin forms a spike-like structure in the renal glomerular basement membrane of normal kidney. Recently, many investigators have suggested that the distribution of laminin in the basement membrane was altered in a variety of renal diseases, expecially in membranous lupus nephritis, membranous proliferative gromerular nephritis, and glomerulosclerosis. To investigate whether the morphologic changes in the glomerulus are associated with the profile of laminin distribution in the renal glomerular basement membrane, the gromerulus was examined after exposure to adriamycin, a potent inducer of nephritis. Male rats(Sprague Dawley strain) were intraperitoneally injected with 0.2ml adriamycin at 25mg/kg body weight. At 24 hour, 48 hour, 72 hour, one week, and 2 week after adriamycin administration, kidney isolated from sacrificed rats was sectioned and observed by immunohistochemical staining and electron microscopy using the immunogold method. The results we obtained were as follows: 1) Renal glomerulus was strongly stained with anti-laminin antibody when 24 or 48 hours passed after adriamycin administration. However, after 1 or 2 weeks later, the antibody response became weak at the level comparable with the vehicle controls. The renal glomerular basement membrane exhibited an increase of gold particles in subjects passed both 24 and 48 hours after adriamycin administration. This increase was observed in mesangial cells in the same subjects. In contrast, both 1 and 2 week-passed subjects displayed a reduction in the binding of gold particles at the level comparable with the vehicle controls. 2) 24 hour-passed rats upon treatment with adriamycin showed various morphologic changes in the renal glomerulus, including thicker and less transparent basement membrane and undetectable lamina densa layer. In conclusion, these results suggest that adriamycin-induced renal toxicity leads to the morphologic alteration along with an increase in laminin expression and that these aspects may be attributable to the regenerative potential of laminin.