title: Calorie restriction decreases platelet-derived growth factor (PDGF)-A and thrombin receptor mRNA expression in autoimmune murine lupus nephritis.
abstract: Calorie restriction (CR) and supplementation with fish oil (FO) are known to increase the life span and diminish histological evidence of glomerulonephritis in lupus prone (NZB x NZW)F1 (B/W) mice. Cellular proliferation is an important pathological element in the development of lupus nephritis, and we have examined the expression of thrombin receptor (TR) and the mitogenic agents PDGF-A and -B. Weanling B/W mice were fed either ad libitum or a calorie restricted (CR; 40% less calories than ad libitum) diet supplemented with either 5% (w/w) corn oil (CO) or FO. CR animals consumed 2.7-3.0 g of wet food per day versus 4.5-5.0 g 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; (ii) in old mice low and similar levels of PDGF-B were detected, and neither CR nor the source of lipid altered its expression; (iii) CR significantly inhibited PDGF-A and TR expression in both CO (ad libitum versus 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 decreased expression, results were not statistically significant. We conclude that suppression of renal disease in lupus-prone mice by CR is accompanied by decreased expression of PDGF-A and the thrombin receptor.
authors.affiliation: Pathology, The University of Texas Health Science Centre, San Antonio 78284-7874, USA.
authors.forename: D A
authors.initials: DA
authors.lastname: Troyer
authors.forename: B
authors.initials: B
authors.lastname: Chandrasekar
authors.forename: J L
authors.initials: JL
authors.lastname: Barnes
authors.forename: G
authors.initials: G
authors.lastname: Fernandes
mesh_terms: D000818:Animals; D015551:Autoimmunity / Q000276:immunology; D004195:Disease Models, Animal; D002149:Energy Intake; D005260:Female; D015870:Gene Expression; D008181:Lupus Nephritis / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D010982:Platelet-Derived Growth Factor / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger; D018179:Receptors, Thrombin / Q000235:genetics / Q000378:metabolism*
chemical_list: D010982:Platelet-Derived Growth Factor; D011518:Proto-Oncogene Proteins; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger; D018179:Receptors, Thrombin; C075278:platelet-derived growth factor A