Effect of glucose on intercellular junctions of cultured human peritoneal mesothelial cells.
During continuous ambulatory peritoneal dialysis, the peritoneum is directly and continuously exposed to unphysiologic peritoneal dialysis fluid; the resulting mesothelial damage has been suggested to cause loss of ultrafiltration and dialysis efficacy. The present study investigated the effect of a high glucose concentration on cultured human peritoneal mesothelial cells to clarify the cause of decreased dialysis efficacy during prolonged peritoneal dialysis. High glucose caused a concentration-dependent decrease in cell proliferation, damage to the intercellular junctions, and excess production of transforming growth factor-beta (TGF-beta). The levels of intercellular junctional proteins (ZO-1, E-cadherin, and beta-catenin) were decreased, and immuno-staining by anti-ZO-1 and anti- beta-catenin antibodies became weaker and often discontinuous along the cell contour. Mannitol had similar but weaker effects at the same osmolality, and an anti-TGF-beta neutralizing antibody reduced the effects of high glucose. Therefore, these effects were induced not only by glucose itself but also by hyperosmolality and by a glucose-induced increase of TGF-beta. These findings suggest that the peritoneal mesothelium is damaged by prolonged peritoneal dialysis using high glucose dialysate and that impairment of the intercellular junctions of peritoneal mesothelial cells by high glucose dialysate induces peritoneal hyperpermeability and a progressive reduction in dialysis efficacy.
Ito
Takafumi
T
Department of Internal Medicine II, Hiroshima University School of Medicine, Hiroshima, Japan.
Yorioka
Noriaki
N
Department of Internal Medicine II, Hiroshima University School of Medicine, Hiroshima, Japan.
Yamamoto
Masao
M
Department of Anatomy II, Hiroshima University School of Medicine, Hiroshima, Japan.
Kataoka
Katsuko
K
Department of Anatomy II, Hiroshima University School of Medicine, Hiroshima, Japan.
Yamakido
Michio
M
Department of Internal Medicine II, Hiroshima University School of Medicine, Hiroshima, Japan.
D000906:Antibodies / Q000494:pharmacology; D015153:Blotting, Western; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003124:Colorimetry; D004847:Epithelial Cells / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D007158:Immunologic Techniques; D007365:Intercellular Junctions / Q000187:drug effects*; D010537:Peritoneum / Q000166:cytology / Q000187:drug effects*; D011994:Recombinant Proteins / Q000494:pharmacology; D013194:Staining and Labeling; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000276:immunology / Q000494:pharmacology; D053773:Transforming Growth Factor beta1
D000906:Antibodies; D011994:Recombinant Proteins; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D005947:Glucose