L-arginine may mediate the therapeutic effects of low protein diets.
We have previously shown beneficial effects of dietary protein restriction on transforming growth factor beta (TGF-beta) expression and glomerular matrix accumulation in experimental glomerulonephritis. We hypothesized that these effects result from restriction of dietary L-arginine intake. Arginine is a precursor for three pathways, the products of which are involved in tissue injury and repair: nitric oxide, an effector molecule in inflammatory and immunological tissue injury; polyamines, which are required for DNA synthesis and cell growth; and proline, which is required for collagen production. Rats were fed six isocaloric diets differing in L-arginine and/or total protein content, starting immediately after induction of glomerulonephritis by injection of an antibody reactive to glomerular mesangial cells. Mesangial cell lysis and monocyte/macrophage infiltration did not differ with diet. However, restriction of dietary L-arginine intake, even when total protein intake was normal, resulted in decreased proteinuria, decreased expression of TGF-beta 1 mRNA and TGF-beta 1 protein, and decreased production and deposition of matrix components. L-Arginine, but not D-arginine, supplementation to low protein diets reversed these effects. These results implicate arginine as a key component in the beneficial effects of low protein diet.
Narita
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I
Division of Nephrology, University of Utah School of Medicine, Salt Lake City 84132, USA.
Border
W A
WA
Ketteler
M
M
Ruoslahti
E
E
Noble
N A
NA
D000818:Animals; D001120:Arginine / Q000494:pharmacology* / Q000627:therapeutic use; D001794:Blood Pressure; D001835:Body Weight; D018753:Diet, Protein-Restricted; D004044:Dietary Proteins; D015870:Gene Expression; D005920:Glomerular Mesangium / Q000378:metabolism* / Q000473:pathology*; D005921:Glomerulonephritis / Q000178:diet therapy* / Q000473:pathology / Q000652:urine; D007106:Immune Sera; D007678:Kidney Glomerulus / Q000378:metabolism / Q000473:pathology; D009573:Nitrites / Q000652:urine; D011507:Proteinuria; D011509:Proteoglycans / Q000096:biosynthesis; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D051381:Rats; D018800:Thy-1 Antigens / Q000276:immunology; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000096:biosynthesis*
D004044:Dietary Proteins; D007106:Immune Sera; D009573:Nitrites; D011509:Proteoglycans; D012333:RNA, Messenger; D018800:Thy-1 Antigens; D016212:Transforming Growth Factor beta; D001120:Arginine