Platelet-derived growth factor in experimental glomerulonephritis

Growth factors and in particular platelet-derived growth factor(PDGF) have been implicated in the pathogenesis of glomerulonephritisand glomerulosclerosis. We have studied the distribution ofimmunoreactive PDGF (iPDGF) within serial kidney biopsies (days7, 15, 30, 90 and 120) of eight rats with an accelerated formof nephrotoxic serum nephritis (NTN). The course of NTN wasmild in five rats and severe in three. Two patterns of immunostainfor PDGF were noted. The first consisted of iPDGF-B chain ina glomerular segmental distribution similar to that of infiltratingmonocytes (OX6+cells). At all stages of NTN the distributionof iPDGF-B chain correlated closely with the immunostain formonocytes. The second pattern of immunostain showed iPDGF-Achain in a diffuse distribution along the glomerular capillarylining and to a lesser extent in some mesangial cells. In severelyaffected rats the magnitude of the iPDGF-A increased along withglomerulosclerosis but disappeared later from areas of segmentaland global glomerular obsolescence. By contrast, in rats withmilder NTN glomerular iPDGF-A chain peaked early and decreasedsubsequently. During the acute phase of NTN, on day 7, iPDGFA chain correlated with the severity of proteinuria (r=0.848,P<0.05) and that of glomerular cellular proliferation (r=0.91,P<0.02). On day 30 iPDGF-B correlated positively with proteinuria(r=0.998, P<0.01, n=5) and with serum creatinine (r=0.949,P<0.02, n=5). During the late stages of NTN, both iPDGF-A(day 90, r=0.884, P<0.05) and iPDGF-B (day 120, r=0.941,P<0.01) correlated closely with the extent of glomerulosclerosis.Both PDGF chains (A and B) are detectable through out the courseof nephrotoxic nephritis in rats. PDGF may play a role in theearly proliferative and late sclerotic changes of experimentalglomerulonephritis.