High glucose inhibits renal proximal tubule cell proliferation and involves PKC, oxidative stress, and TGF-beta 1.
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.
Park
S H
SH
Department of Veterinary Physiology, College of Veterinary Medicine, Hormone Research Center, Chonnam National University, Kwangju, Korea.
Choi
H J
HJ
Lee
J H
JH
Woo
C H
CH
Kim
J H
JH
Han
H J
HJ
D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003928:Diabetic Nephropathies / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D005947:Glucose / Q000494:pharmacology*; D007687:Kidney Tubules, Proximal / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D007930:Leucine / Q000378:metabolism; D008054:Lipid Peroxides / Q000096:biosynthesis; D018384:Oxidative Stress / Q000187:drug effects; D011493:Protein Kinase C / Q000378:metabolism; D011817:Rabbits; D013654:Taurine / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014810:Vitamin E / Q000494:pharmacology
D000975:Antioxidants; D008054:Lipid Peroxides; D016212:Transforming Growth Factor beta; D014810:Vitamin E; D013654:Taurine; D011493:Protein Kinase C; D007930:Leucine; D005947:Glucose; D013936:Thymidine; D000111:Acetylcysteine