Transforming growth factor-beta expression in macrophages during hypercholesterolemic states.
Macrophage infiltration into the glomerular mesangium is a prominent feature of various glomerulopathies. Recent evidence suggests that infiltrating macrophages may play a role in propagating initial glomerular injury to the development of glomerulosclerosis via transforming growth factor-beta (TGF-beta)-stimulating matrix accumulation. Rats with the acute puromycin aminonucleoside (PA) nephrosis exhibit an elevated gene expression of glomerular TGF-beta 1; however, the cellular origin of this upregulation is unknown. Using polymerase chain reaction (PCR), we detected that the TGF-beta 1 isoform is expressed in glomerular macrophages isolated from experimental rats made hypercholesterolemic by either diet or by induction of PA nephrosis. Peritoneal macrophages from nephrotic or dietary-hypercholesterolemic animals also exhibited a significant increment in the expression of TGF-beta 1 mRNA on Northern analysis, in contrast to similar cells obtained from normal control rats. PCR analysis of glomerular RNA also detected the expression of the TGF-beta 2 mRNA isoform. TGF-beta 2 mRNA expression was not observed in isolated glomerular macrophages from either glomeruli of PA-nephrotic rats or from glomeruli of animals with dietary hypercholesterolemia. Expression of the TGF-beta 3 mRNA isoform was only observed by PCR in J774 A.1 cells. Thus the as a cellular source for the enhanced expression of TGF-beta 1 during the acute nephrotic phase of our toxic, progressive glomerulopathy model and within several days of inducing only hypercholesterolemia by dietary means.
Ding
G
G
Department of Medicine, Milton S. Hershey Medical Center, Hershey, Pennsylvania.
van Goor
H
H
Frye
J
J
Diamond
J R
JR
D000419:Albuminuria; D000818:Animals; D001483:Base Sequence; D002791:Cholesterol, Dietary / Q000008:administration & dosage; D015870:Gene Expression; D006937:Hypercholesterolemia / Q000209:etiology / Q000378:metabolism*; D007150:Immunohistochemistry; D007678:Kidney Glomerulus / Q000473:pathology; D008055:Lipids / Q000097:blood; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D008969:Molecular Sequence Data; D009401:Nephrosis / Q000139:chemically induced / Q000150:complications / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011692:Puromycin Aminonucleoside; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016212:Transforming Growth Factor beta / Q000235:genetics*
D002791:Cholesterol, Dietary; D008055:Lipids; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D011692:Puromycin Aminonucleoside