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

摘要

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.