Thy1 glomerulonephritis induced in young Lewis rats accelerates age-related glomerulosclerosis

Age-related and disease-induced glomerulosclerosis (GS) in rats have both b een well defined in a number of strains and experimental models, but the in ter-relationship between the two is not clear. The present study was undert aken to compare the pattern of glomerular injury in these two types of GS. One- and two-shot Thy1 glomerulonephritis (GN) was induced at 2 months of a ge and followed for 12 months. At 12 months histological injury in proteinu ric rats was characterized by segmental hyaline lesions. Two-shot Thy1 GN r esulted in accelerated, but morphologically identical injury at 8 months. H istological lesions predictive of subsequent accelerated GS were evaluated at 1, 2, 4 and 6 months. In this regard, glomerular hypercellularity, rathe r than hypertrophy or matrix increase, was the most consistent histological index of later accelerated disease. The profibrotic cytokines transforming growth factor (TGF)-beta (1) and -beta (3) were localized distinctly to se gmental hyaline lesions, but not to areas of matrix increase within the glo merular tuft. This study reveals that GS after Thy1 GN represents accelerat ion of an age-related disease, presents evidence for use of prolonged glome rular hypercellularity as the best histological index of future disease pro gression, and correlates the key lesion of GS in these animals, the segment al hyaline lesion, with the presence of TGF-beta peptides. Copyright (C) 20 01 S. Karger AG, Basel.