Effect of glucose on intercellular junctions of cultured human peritoneal mesothelial cells

During continuous ambulatory peritoneal dialysis, the peritoneum is directl y and continuously exposed to unphysiologic peritoneal dialysis fluid; the resulting mesothelial damage has been suggested to cause loss of ultrafiltr ation 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 perito neal dialysis. High glucose caused a concentration-dependent decrease ill c ell proliferation, damage to the intercellular junctions, and excess produc tion of transforming growth factor-beta (TGF-beta). The levels of intercell ular junctional proteins (ZO-1, E-cadherin, and beta -catenin) were decreas ed, and immuno-staining by anti-ZO-1 and anti-beta -catenin antibodies beca me weaker and often discontinuous along the cell contour. Mannitol had simi lar but weaker effects at the same osmolality, and an anti-TGF-beta neutral izing antibody reduced the effects of high glucose. Therefore, these effect s were induced not only by glucose itself but also by hyperosmolality and b y a glucose-induced increase of TGF-beta. These findings suggest that the p eritoneal mesothelium is damaged by prolonged peritoneal dialysis using hig h glucose dialysate and that impairment of the intercellular junctions of p eritoneal mesothelial cells by high glucose dialysate induces peritoneal hy perpermeability and a progressive reduction in dialysis efficacy.