The present finding demonstrate that HG stimulates TGF-beta 1 very early and prior to FN production and that HG-induced FN production is mediated by TGF-beta. This finding is consistent with the view that TGF-beta mediates increased ECM accumulation by MC under high glucose conditions.

Objective The effect of long-term use of high glucose dialysate on peritoneal structure and function, and its relation with accumulation of advanced glycosylation end-product (AGE) in the peritoneum was investigated in this study. Methods Dialysates with 4.25% glucose were injected into the peritoneal cavity of normal rats for 12 weeks without (PD, n = 7) and with (1 g/L, PD+AG, n = 7) aminoguanidine in their drinking water. Rats not having intraperitoneal (IP) injection served as control ( n = 9). After 12 weeks of IP injection, a 2-hour peritoneal equilibration test (PET) was performed using 30 mL 4.25% glucose dialysate. Intraperitoneal volume (IPV), dialysate-to-plasma urea ratio at 2 hours (D2/P2), the ratio of dialysate glucose at 2 hours to initial dialysate glucose (D2/D0), and the peritoneal fluid absorption rate (Qa) were evaluated. After the PET, samples of the parietal peritoneum were taken for hematoxylin and eosin (H&E) staining and immunohistochemical staining for AGE. Results The IPV and D2/D0 glucose were significantly lower and Qa and D2/P2 urea significantly higher in the PD group than in the control group. Aminoguanidine reversed in part the changes in IPV and D2/P2 urea in the PD group; it had no effect on Qa and D2/D0 glucose. The H&E staining showed a linear mesothelial lining with negligible cells and capillaries in the narrow submesothelial space in the control group. Mesothelial denudation and submesothelial infiltration of monocytes and capillary formation were observed in the PD group. Mesothelial denudation was relatively intact in the PD+AG group compared with the PD group. Submesothelial monocyte infiltration and capillary formation in the PD+AG group were not as prominent as in the PD group. Positive AGE staining was found in the submesothelial space, vascular walls, and endomysium in the PD group, while it was markedly attenuated in PD+AG group and negligible in the control group. Conclusion Long-term use of high glucose solutions induced peritoneal AGE accumulation and mesothelial denudation, and increased peritoneal permeability and peritoneal fluid absorption rate. Inhibition of peritoneal AGE accumulation prevented those functional and structural damages to the peritoneum.