Protective Role of the Natriuretic Peptide System in Tissue Injury and Remodeling

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In prder to explore the rote of natriuretic peptides, with potent diuretic and vasorelaxing properties, in tissue injury and remodeling, we investigated the effect of chronic excess of brain natriuretic peptide (BNP) in transgenic mice on renal injuries using various nephropathy modelsIn a model of anti-glomerular-basement-membrane antibody glomerulonephritis (GN), control nontransgenic mice developed progressive GN with heavy prateinuria (21 times of baseline level) and severe glomerular/tubulointerstitial damage at 8-12 weeks. In contrast, BNP-transgenic mice (BNP-Tg) showed only minor and transient proteinuria with no apparent tissue damage. Gene expression of transforming growth factorβ (TGF-β) and monocyte chemoattractant protein-1 (MCP-1) as well as the activation of ERK/MAP kinase within renal tissues was much reduced in BNP-Tg, suggesting that these worked together to ameliorate renal injuriesIn a model of renal fibrosis with unilateral ureteral obstruction (UUO), interstitial … More fibrosis was significantly ameliorated in BNP-Tg as compared with control nontransgenic mice. TGF-β expresstan was much reduced in BNP-Tg. Subsequent analysis revealed that the blood fbw in the renal peritubular capillary was significantly maintained in BNP-Tg, suggesting that such mechanisms of vascular protection may act against the progression of fibrotic processesIn a model of diabetic nephropathy, control mice developed significant proteinuria with masangial expansion 16 weeks after the onset of streptozotocin-induced diabetes. These changes were significantly milder in BNP-Tg. BNP inhibited the mesangial up regulation of TGF-β in vivo and in vitro, suggesting that this may provide a common key mechanism of renoprotectionThese results indicate that natriuretic peptides potentially exert renoprotective effects by counteracting the fibrogenic stimuli such as TGF-βand MCP-1, suggesting that the activation of the natriuretic peptide system should be clinically applicable against various nephropathies Less