Functional and structural alterations of peritoneum and secretion of fibrotic cytokines in rats caused by high glucose peritoneal dialysis solutions

Abstract

Objective: To determine functional and structural alterations of peritoneum and fibrotic cytokines expression in peritoneal dialysis (PD) rats. Methods: 28 Sprague-Dawley (S-D) rats were randomly divided into four groups and dialyzed with various solutions daily for four weeks: (1) no solution (CON group), (2) 0.9% Saline solution (NS group), (3) 1.5% Dianeal (LG group), (4) 4.25% Dianeal (HG group). Peritoneal equilibration tests, ultrafiltration function and effluent protein quantification were measured. Peritoneum morphology was studied and immunohistochemistry were performed for detection of transforming growth factor b1 (TGF-b1), connective tissue growth factor (CTGF), and fibronectin (FN) proteins. Reverse transcriptional-polymerase chain reaction was used to analyze the expression of TGF-b1, CTGF mRNA. Results: Administration of 4.25% Dianeal caused functional and structural changes of peritoneum, including protein loss through the transport process, decrease of peritoneal solute transport rate and ultrafiltration capacity. The collagen of peritoneum in the HG group was thicker than the other groups. The levels of CTGF, TGF-b1, and FN proteins were significantly the highest in the HG group, followed by the LG group. The liner correlation analysis showed positive correlations between the levels of CTGF, TGF-b1, and FN proteins and the collagen thickness. The expression of TGF-b1 and CTGF mRNA in the HG group were significantly higher than those in the other groups and were indicated positive correlation.

Telmisartan attenuates peritoneal fibrosis via peroxisome proliferator‐activated receptor‐γ activation in rats

“…[29][30][31] Therefore, the expressions of ECM proteins and hallmarks of fibroblast acti- vation were also investigated in the present study. In accordance with a previous study, 32 we found TGF-b was significantly elevated in PD rats and high glucose-induced rat PMC. Meanwhile, the expression of FN and Col-I were upregulated in the peritoneum of rats, which thereby induced PF.…”

Peritoneal inflammation and fibrosis in C‐reactive protein transgenic mice undergoing peritoneal dialysis solution treatment

“…In vitro studies showed that CTGF expression in human peritoneal mesothelial cells (HPMCs) was increased by PD treatment . Glucose in the PD solution was shown to be the factor responsible for the increase in CTGF expression . Our present study shows that CRP is another factor causes the increase in CTGF expression.…”

Suramin Inhibits the Development and Progression of Peritoneal Fibrosis

“…However, the duration of PD can be limited by peritoneal alteration in both structure and function, including peritoneal fibrosis and ultrafiltration failure (Saxena, 2008;Davies et al, 2011). In vitro and in vivo studies (Liu et al, 2014) have demonstrated that peritoneal fibrosis is characterized by detachment of the mesothelial layer, dilatation of intercellular spaces, and deposition of extracellular matrix (Devuyst et al, 2010). Our current studies have also shown that suramin can inhibit submesothelial thickening, deposition of fibrils, and expression of multiple ECM proteins, suggesting its usefulness in attenuating peritoneal fibrosis and reducing ultrafiltration failure.…”