高糖抑制肾近端小管细胞增殖，并涉及蛋白激酶C、氧化应激和转化生长因子-β1。
High glucose inhibits renal proximal tubule cell proliferation and involves PKC, oxidative stress, and TGF-beta 1.
作者信息
Park S H, Choi H J, Lee J H, Woo C H, Kim J H, Han H J
机构信息
Department of Veterinary Physiology, College of Veterinary Medicine, Hormone Research Center, Chonnam National University, Kwangju, Korea.
出版信息
Kidney Int. 2001 May;59(5):1695-705. doi: 10.1046/j.1523-1755.2001.0590051695.x.
BACKGROUND
The alteration of renal cell growth is one of the early abnormalities in the diabetic nephropathy. However, the effects of high glucose and its action mechanism in renal proximal tubule cell (PTC) proliferation have not been elucidated.
METHODS
The effects of 25 mmol/L glucose on cell proliferation, thymidine, and leucine incorporation, cell cycle, and lipid peroxide formation were examined in the primary cultured renal PTCs.
RESULTS
Glucose 25 mmol/L inhibited [3H]-thymidine incorporation and decreased cell growth. However, it increased [3H]-leucine incorporation and protein content. Furthermore, 25 mmol/L glucose increased lipid peroxide formation. These effects of glucose were blocked by antioxidants, vitamin E, N-acetylcystein, or taurine. Staurosporine and H-7 totally blocked 25 mmol/L glucose-induced lipid peroxide formation and had an inhibitory effect on [3H]-thymidine incorporation. Indeed, 25 mmol/L glucose increased the translocation of protein kinase C (PKC) from cytosolic fraction to membrane fraction. In addition, high glucose increased the secretion of transforming growth factor-beta1 (TGF-beta 1) via the PKC-oxidative stress pathway, and TGF-beta 1 inhibited [3H]-thymidine incorporation in a dose-dependent manner.
CONCLUSIONS
High glucose inhibits renal PTC proliferation via PKC, oxidative stress, and the TGF-beta 1 signaling pathway.
背景
肾细胞生长改变是糖尿病肾病早期异常之一。然而，高糖对肾近端小管细胞（PTC）增殖的影响及其作用机制尚未阐明。
方法
检测25 mmol/L葡萄糖对原代培养的肾PTC细胞增殖、胸苷和亮氨酸掺入、细胞周期及脂质过氧化物形成的影响。
结果
25 mmol/L葡萄糖抑制[3H]-胸苷掺入并降低细胞生长。然而，它增加了[3H]-亮氨酸掺入和蛋白质含量。此外，25 mmol/L葡萄糖增加脂质过氧化物形成。葡萄糖的这些作用被抗氧化剂、维生素E、N-乙酰半胱氨酸或牛磺酸阻断。星形孢菌素和H-7完全阻断25 mmol/L葡萄糖诱导的脂质过氧化物形成，并对[3H]-胸苷掺入有抑制作用。实际上，25 mmol/L葡萄糖增加了蛋白激酶C（PKC）从胞质组分向膜组分的转位。此外，高糖通过PKC-氧化应激途径增加转化生长因子-β1（TGF-β1）的分泌，且TGF-β1以剂量依赖方式抑制[3H]-胸苷掺入。
结论
高糖通过PKC、氧化应激和TGF-β1信号通路抑制肾PTC增殖。
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