Ying W Z, Sanders P W
Nephrology Research and Training Center, University of Alabama at Birmingham 35294-0007, USA.
Am J Physiol. 1998 Apr;274(4):F635-41. doi: 10.1152/ajprenal.1998.274.4.F635.
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.
转化生长因子（TGF）是一类强大的多功能多肽，参与肾功能和肾小球硬化过程。我们推测饮食中的盐会改变肾脏中TGF-β的产生。饮食中盐的增加导致大鼠肾脏中TGF-β1、-β2和-β3的mRNA稳态水平持续升高。虽然TGF-β1的血清浓度没有变化，但8.0%氯化钠饮食增加了TGF-β1的尿排泄，表明肾脏产生增加是TGF-β1的来源。用利尿剂增加尿流率并没有进一步增加接受8.0%氯化钠饮食动物的TGF-β1合成。8.0%氯化钠饮食增加了肾小球和肾小管中TGF-β1的产生，尽管活性TGF-β1仅从肾小球中分泌出更多量。8.0%氯化钠饮食诱导的无活性和活性TGF-β1在肾小球中的产生增加被四乙铵（TEA）抑制，而不是格列本脲。8.0%氯化钠饮食时心脏中TGF-β1的产生也增加，但不受TEA影响。结果表明，饮食中盐的增加通过一种包括TEA敏感钾通道的机制增强了肾小球TGF-β的产生。饮食中的盐通过促进TGF-β在肾小球中的表达，可能直接促进肾小球硬化的发展。
