RELATIONSHIP BETWEEN VIMENTIN EXPRESSING RENAL TUBULES AND INTERSTITIAL FIBROSIS IN CHRONIC PROGRESSIVE NEPHROPATHY IN AGED RATS

We investigated the relationship between regenerating renal tubular ep ithelial cells and myofibroblast development in chronic progressive ne phropathy (CPN) of aged male F344 rats. We used established criteria t o classify disease in rats with CPN as grade 1 (n=9), grade 2 (n=10), grade 3 (n=7) and grade 4 (n=4). Five young rats served as controls (g rade 0). The ratio of fibrotic tissues per unit area, assessed in coll agen type III-immunostained sections by morphometric analysis, increas ed significantly with advancing grade of CPN. Vimentin-expressing, reg enerating renal tubules were found from grade 1 and continued to incre ase in number up to grade 3, decreasing slightly, however, in grade 4. Similar kinetics were seen for the number of a-smooth muscle actin-po sitive myofibroblasts, and there was a significant correlation between the number of regenerating renal tubules and myofibroblast developmen t (correlation coefficient=0.83, P<0.01). The myofibroblasts developed in close association with the fibrotic areas seen in grades 1-4; the cells also reacted to desmin or vimentin, indicating the activated sta te. Immunohistochemistry for platelet-derived growth factor (PDGF)-BB and transforming growth factor (TGF)-beta revealed that vimentin-posit ive renal tubules were positive for PDGF-BB, but negative for TGF-beta , and that interstitial reactive cells showed no positive reactions fo r both factors. The present studies on rat CPN showed that regeneratin g renal tubules may be a major source of a fibrogenic growth factor, P DGF-BB, and that the PDGF-BB might induce the development of fibrogeni c cells, myofibroblasts, culminating in progressive interstitial fibro sis.