Expression of PDGF alpha-receptor in renal arteriosclerosis and rejecting renal transplants.

Abstract

Platelet-derived growth factor (PDGF) plays an important role in renal disease. We have recently demonstrated that in healthy mature human kidney, PDGF alpha-receptor expression is largely restricted to interstitial cells. The study presented here assesses the expression of PDGF alpha-receptor in 18 mature adult kidneys with arteriosclerosis from individuals with no clinically evident history of renal disease other than localized neoplasia, in 13 kidneys with irreversible transplant rejection, and in a series of renal transplant biopsies composed of examples of both severe and absent rejection, by in situ hybridization and immunocytochemistry. Strong focal or diffuse expression of PDGF alpha-receptor mRNA and protein was noted in some intimal cells of intrarenal arterial vessels exhibiting signs of arteriosclerosis and/or vascular rejection. By double immunostaining, it could be shown that these cells were neither endothelial cells nor infiltrating leukocytes. The cells were most often identified as smooth muscle by colabeling for the smooth muscle cell-specific protein SM22alpha and less commonly for alpha-smooth muscle actin. There was also a population of PDGF alpha-receptor-expressing cells that failed to colabel with any of these markers, and hence remain of uncertain histogenesis. These intimal cells were generally negative for several other markers of differentiated smooth muscle cells, i.e., calponin and desmin. Near these PDGF alpha-receptor-positive intimal cells, expression of PDGF A-chain, an alpha-receptor ligand, was demonstrated in endothelial, intimal, and/or medial cells. Prominent PDGF alpha-receptor mRNA and protein expression also was noted in areas of interstitial fibrosis and in some glomeruli, in particular those with segmental glomerulosclerosis or fibrotic crescents. Double immunolabeling for PDGF alpha-receptor and alpha-smooth muscle actin confirmed that most of these latter PDGF alpha-receptor-positive cells were interstitial myofibroblasts or mesangial cells, or both. In summary, these data demonstrate widespread expression of PDGF alpha-receptor in renal cell types involved in fibrotic and sclerosing processes. The data also show that PDGF alpha-receptor expression identifies a unique population of phenotypically altered vascular smooth muscle cells, which appear to be involved in the vascular response to injury.