PLATELET-DERIVED GROWTH-FACTOR IN EXPERIMENTAL GLOMERULONEPHRITIS

Growth factors and in particular platelet-derived growth factor (PDGF) have been implicated in the pathogenesis of glomerulonephritis and glomerulosclerosis. We have studied the distribution of immunoreactive PDGF (iPDGF) within serial kidney biopsies (days 7, 15, 30, 90 and 120) of eight rats with an accelerated form of nephrotoxic serum nephritis (NTN). The course of NTN was mild in five rats and severe in three. Two patterns of immunostain for PDGF were noted. The first consisted of iPDGF-B chain in a glomerular segmental distribution similar to that of infiltrating monocytes (OX6+cells). At all stages of NTN the distribution of iPDGF-B chain correlated closely with the immunostain for monocytes. The second pattern of immunostain showed iPDGF-A chain in a diffuse distribution along the glomerular capillary lining and to a lesser extent in some mesangial cells. In severely affected rats the magnitude of the iPDGF-A increased along with glomerulosclerosis but disappeared later from areas of segmental and global glomerular obsolescence. By contrast, in rats with milder NTN glomerular iPDGF-A chain peaked early and decreased subsequently. During the acute phase of NTN, on day 7, iPDGF A 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 throughout the course of nephrotoxic nephritis in rats. PDGF may play a role in the early proliferative and late sclerotic changes of experimental glomerulonephritis.