CALORIE RESTRICTION DECREASES PLATELET-DERIVED GROWTH-FACTOR (PDGF)-AAND THROMBIN RECEPTOR MESSENGER-RNA EXPRESSION IN AUTOIMMUNE MURINE LUPUS NEPHRITIS

Calorie restriction (CR) and supplementation with fish oil (FO) are kn own to increase the life span and diminish histological evidence of gl omerulonephritis in lupus prone (NZB x NZW)F-1 (B/W) mice. Cellular pr oliferation is an important pathological element in the development of lupus nephritis, and we have examined the expression of thrombin rece ptor (TR) and the mitogenic agents PDGF-A and -B. Weanling B/W mice we re fed either ad libitum or a calorie restricted (CR; 40% less calorie s than ad libitum) diet supplemented with either 5% (w/w) corn oil (CO ) or FO. CR animals consumed 2.7-3.0g of wet food per day versus 4.5-5 .0g for the ad libitum animals. Renal RNA was extracted from young (3. 5-4.0 months of age) and old (8-10 months of age) mice. Densitometric analysis (reference gene GAPDH) of blots from Northern (PDGF-A and -B) and ribonuclease protection assays (TR) produced the following data: (i) in young mice no signal was detected for PDGF-A, -B and TR in all four groups, while the signals were readily detectable in old mice; (i i) in old mice low and similar levels of PDGF-B were detected, and nei ther CR nor the source of lipid altered its expression; (iii) CR signi ficantly inhibited PDGF-A and TR expression in both CO (ad libitum ver sus CR; PDGF-A, 3.25-fold, P < 0.025; TR, 3.7-fold, P < 0.01) and FO ( ad libitum versus CR; PDGF-A, 4.56-fold, P < 0.01; TR, 3.6-fold, P < 0 .025) groups; (iv) although FO (versus CO) produced a trend towards de creased expression, results were not statistically significant. We con clude that suppression of renal disease in lupus-prone mice by CR is a ccompanied by decreased expression of PDGF-A and the thrombin receptor .