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Kidney Int Suppl. 2005 Dec;(99):S98-102.

Tumor necrosis factor-alpha gene expression in diabetic nephropathy: relationship with urinary albumin excretion and effect of angiotensin-converting enzyme inhibition.

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1
Servicio de Nefrología, Unidad de Investigación, y Servicio de Bioquímica Clínica, Hospital Universitario Nuestra Señora de Candelaria, Tenerife, Spain. jnavgon@gobiernodecanarias.org

Abstract

BACKGROUND:

The pathogenic mechanisms and molecular events involved in the development and progression of diabetic nephropathy (DN) are not completely known. Recent data indicate that diabetes includes an inflammatory component that is related to diabetic complications. Tumor necrosis factor (TNF)-alpha, a cytokine with mainly proinflammatory activity, may be synthesized by renal cells. Our objective was to analyze intrarenal TNF-alpha gene expression and its relationship with urinary albumin excretion (UAE). We also investigated the effect of inhibition of angiotensin-converting enzyme on TNF-alpha expression and UAE.

METHODS:

Streptozotocin-induced diabetic rats received either no treatment or an angiotensin-converting enzyme inhibitor (enalapril). After eight weeks, renal expression of TNF-alpha was evaluated by real-time polymerase chain reaction.

RESULTS:

Renal cortical messenger RNA levels of TNF-alpha increased significantly and were twice as high in diabetic rats than in nondiabetic control rats. Enalapril administration nearly completely abolished the increase in TNF-alpha messenger RNA expression to the level observed in control rats. UAE was significantly correlated with urinary levels of TNF-alpha (r=0.68, P<0.05) and with renal TNF-alpha expression (r=0.51, P<0.05).

CONCLUSION:

DN was associated with increased renal expression of TNF-alpha and UAE. Enalapril administration prevented this enhanced expression of TNF-alpha and decreased urinary cytokine excretion and albuminuria. These data provide a novel insight into the pathogenic mechanisms of DN, and support the hypothesis that inflammatory mechanisms may play a significant role in the development and progression of renal injury secondary to diabetes mellitus.

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