High glucose inhibits renal proximal tubule cell proliferation and involves PKC, oxidative stress, and TGF-beta 1.

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. 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. 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. High glucose inhibits renal PTC proliferation via PKC, oxidative stress, and the TGF-beta 1 signaling pathway.