Effect of high glucose on peritoneal mesothelial cell biology.
OBJECTIVE
This study reviews evidence that implicates high glucose (HG) in the pathogenesis of peritoneal fibrosis and proposes mechanisms potentially involved in the HG-induced peritoneal fibrosis that is observed in long-term peritoneal dialysis (PD) patients.


METHODS
Selected Western literature is reviewed, examining the effect of HG on rat or human peritoneal mesothelial cell (HPMC) biology with particular reference to extracellular matrix (ECM) gene expression and protein synthesis.


RESULTS
HG up-regulated the expression of monocyte chemotactic peptide-1 (MCP-1), transforming growth factor beta 1 (TGF beta 1), and fibronectin messenger RNAs (mRNAs) and proteins. These HG-induced up-regulations were effectively blocked by the inhibition of protein kinase C (PKC). In addition, cytosolic reactive oxygen species (ROS) rapidly increased in HPMC cultured under HG, and treatment with antioxidant effectively inhibited HG-induced fibronectin protein synthesis by HPMC.


CONCLUSIONS
Continuous exposure of the peritoneal membrane to HG may induce changes in HPMC biology, leading to excessive deposition of ECM and peritoneal injury. HG-induced activation of diacylglycerol PKC (DAG-PKC) plays a major role in up-regulation of MCP-1, TGF beta 1, and fibronectin synthesis by HPMC cultured under HG. In addition, ROS, recently recognized as signalling molecules, are rapidly generated in HPMC as a result of increased glucose metabolism and may prove to be an important mediator of HG-induced peritoneal injury.
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Department of Pharmacology, Yonsei University College of Medicine, Seoul, Korea.
Lee
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D000818:Animals; D018932:Chemokine CCL2 / Q000378:metabolism; D015314:Dialysis Solutions / Q000633:toxicity; D004847:Epithelial Cells / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism; D005355:Fibrosis / Q000139:chemically induced; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D010530:Peritoneal Dialysis; D010537:Peritoneum / Q000166:cytology / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D015854:Up-Regulation
D018932:Chemokine CCL2; D015314:Dialysis Solutions; D005353:Fibronectins; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D016212:Transforming Growth Factor beta; D011493:Protein Kinase C; D005947:Glucose