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  • Title: Alteration of growth-related proto-oncogene expression in diabetic glomeruli by a specific endothelin receptor A antagonist.
    Author: Nakamura T, Ebihara I, Tomino Y, Koide H.
    Journal: Nephrol Dial Transplant; 1996 Aug; 11(8):1528-31. PubMed ID: 8856205.
    Abstract:
    BACKGROUND: The early phase of glomerular growth in diabetic rats is accompanied by increased c-fos and c-jun expression. The renal endothelin (ET)-1 mRNA levels increased with the progression of diabetic nephropathy. This study was designed to assess whether glomerular mRNA expression of growth-related proto-oncogenes in diabetic rat glomeruli is affected by a specific ET receptor A antagonist, FR139317. METHODS: Diabetes was produced by streptozotocin (STZ) injection. Animals were divided into four groups: (1) untreated diabetic rats (n = 25); (2) FR139317-treated diabetic rats (n = 20); (3) control non-diabetic rats (n = 20); and (4) FR139317-treated controls (n = 20). FR139317 treatment was continued for 24 weeks. c-myc, c-fos, c-jun and proliferating cell nuclear antigen (PCNA) mRNA expression in rat glomeruli from each group (n = 7) at 4, 12 and 24 weeks after STZ or saline injection was evaluated. RESULTS: Glomerular mRNA levels for c-myc, c-fos, c-jun and PCNA in group 1 increased with the progression of diabetic nephropathy (24 weeks: c-myc, 4.6-fold; c-fos, 3.8-fold; c-jun, 4.2-fold; and PCNA, 4.4-fold). FR139317 treatment attenuated increases in glomerular mRNA levels of these genes (24 weeks, c-myc, 0.4-fold; c-fos, 0.4-fold; c-jun, 0.5-fold; and PCNA, 0.4-fold) in group 2. However, FR139317 did not affect mRNA levels in control glomeruli. CONCLUSIONS: These data suggest that FR139317 may protect against glomerular injury of diabetes in rats by reducing mRNA levels of growth-related genes.
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