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Am J Physiol. 1998 Apr;274(4 Pt 2):F635-41.

Dietary salt modulates renal production of transforming growth factor-beta in rats.

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Nephrology Research and Training Center, University of Alabama at Birmingham 35294-0007, USA.


Transforming growth factors (TGF) are potent multifunctional polypeptides that are involved in renal function and glomerular sclerosis. We postulated that dietary salt modified renal production of TGF-beta. An increase in dietary salt produced sustained increases in steady-state levels of mRNA for TGF-beta 1, -beta 2, and -beta 3 in the rat kidney. While serum concentration of TGF-beta 1 did not change, the 8.0% NaCl diet increased urinary excretion of TGF-beta 1, indicating enhanced renal production was the source of TGF-beta 1. Increasing urinary flow rates with diuretics did not further increase synthesis of TGF-beta 1 in animals receiving the 8.0% NaCl diet. The 8.0% NaCl diet increased production of TGF-beta 1 in both glomeruli and tubules, although active TGF-beta 1 was secreted in greater amounts only from glomeruli. Enhanced glomerular production of both inactive and active TGF-beta 1 induced by the 8.0% NaCl diet was inhibited by tetraethylammonium (TEA) and not glybenclamide. Cardiac production of TGF-beta 1 also increased on the 8.0% NaCl diet but was not affected by TEA. The results demonstrated that increased dietary salt augmented glomerular TGF-beta production by a mechanism that included a TEA-sensitive potassium channel. Dietary salt, by facilitating glomerular expression of TGF-beta, may directly promote development of glomerulosclerosis.

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