TRANSFORMING GROWTH-FACTOR-BETA EXPRESSION IN MACROPHAGES DURING HYPERCHOLESTEROLEMIC STATES

Macrophage infiltration into the glomerular lar mesangium is a promine nt feature of various glomerulopathies. Recent evidence suggests that infiltrating macrophages may play a role in propagating initial glomer ular injury to the development of glomerulosclerosis via transforming growth factor-beta (TGF-beta)-stimulating matrix accumulation. Rats wi th the acute puromycin aminonucleoside (PA) nephrosis exhibit an eleva ted gene expression of glomerular TGF-beta 1; however, the cellular or igin of this upregulation is unknown. Using polymerase chain reaction (PCR), we detected that the TGF-beta 1 isoform is expressed in glomeru lar macrophages isolated from experimental rats made hypercholesterole mic by either diet or by induction of PA nephrosis. Peritoneal macroph ages from nephrotic or dietary-hypercholesterolemic animals also exhib ited a significant increment in the expression of TGF-beta 1 mRNA on N orthern analysis, in contrast to similar cells obtained from normal co ntrol rats. PCR analysis of glomerular RNA also detected the expressio n of the TGF-beta 2 mRNA isoform. TGF-beta 2 mRNA expression was not o bserved in isolated glomerular macrophages from either glomeruli of PA -nephrotic rats or from glomeruli of animals with dietary hypercholest erolemia. Expression of the TGF-beta 3 mRNA isoform was only observed by PCR in J774 A.1 cells. Thus the present study identified the infilt rating glomerular macrophage as a cellular source for the enhanced exp ression of TGF-beta 1 during the acute nephrotic phase of our toxic, p rogressive glomerulopathy model and within several days of inducing on ly hypercholesterolemia by dietary means.