Inhibiting effect of short hairpin RNA on expression of transforming growth factor-β1 in human peritoneal mesothelial cells induced by peritoneal dialysis solution

The peritoneum response to peritoneal dialysis can lead to fibrosis. The transforming growth factor-β1 （TGF-β1） plays an important role in regulating tissue repair and remodeling after injury. Excessive synthesis and deposition of matrix proteins by peritoneal mesothelial cells can lead to structural and functional changes in the peritoneal membrane, jeopardizing the long-term efficacy of peritoneal dialysis （PD）. Prolonged exposure to high glucose concentrations in PD fluid has been implicated as a major stimulus to matrix accumulation, through the induction of transforming growth factor-β1 （TGF-β1）.

Effect of Ligustrazine Nanoparticles Nano Spray on Transforming Growth Factor-β/Smad Signal Pathway of Rat Peritoneal Mesothelial Cells Induced by Tumor Necrosis Factor-α

Objective： To study the effect of ligustrazine nanoparticles nano spray（LNNS） on transforming growth factor β（TGF-β）/Smad signal protein of rat peritoneal mesothelial cells（RPMC） induced by tumor necrosis factor α（TNF-α）, and the anti-adhesion mechanism of LNNS in the abdominal cavity. Methods： The primary culture and subculture of rat peritoneal mesothelial cells（RPMC） was processed by trypsin digestion method in vitro. The third generation was identified for experiment and divided into 5 groups： a blank group： RPMC without treatment; a control group： RPMC stimulated with TNF-α; RPMC treated by a low-dosage LNNS group（2.5 mg/L）; RPMC treated by a medium-dosage LNNS group（5 mg/L）; and RPMC treated by a high-dosage LNNS group（10 mg/L）. Reverse transcription-polymerase chain reaction was applied to test the expression of fibronectin, collagen Ⅰ（COL-Ⅰ）, TGF-β m RNA, and Western blot method to test the Smad protein 7 expression of RPMC. Results： Compared with the blank group, a significant elevation in fibronectin（FN）, COL-Ⅰ and TGF-β m RNA expression of RPMC were observed in the control group（P〈0.05）. Compared with the control group, LNNS suppressed the expressions of FN, COL-Ⅰ and TGF-β m RNA in a concentrationdependent manner（P〈0.05）. The expression of Smad7 protein of RPMC was down-regulated by TNF-α stimulation, and up-regulated with the increase of LNNS dose（P〈0.05）. Conclusions： TNF-α may induce changes in RPMC＇s viability, leading to peritoneal injury. LNNS could reverse the induction of fibrosis related cytokine FN, COL-Ⅰ and TGF-β, up-regulating the expression of Smad7 by TNF-α in RPMC, thus attenuate peritoneal injury by repairing mesothelial cells.

Morphological changes of the peritoneum in peritoneal dialysis patients

Background Long-term peritoneal dialysis (PD) requires that the peritoneal membrane remain effective for dialysis. Research directed toward human peritoneal morphology and structure is limited. The present study was performed to investigate morphological changes of the human peritoneal membrane during PD and to elucidate the possible mechanisms of its functional deterioration. Methods A total of 32 peritoneal biopsies were performed in normal subjects (n=10),uremic nondialysis patients (n=12) at the time of catheter insertion,and PD patients (n=10) at the time of catheter removal or reinsertion or at the time of renal transplantation. Peritoneal morphology was examined by light microscopy,scanning electron microscopy,and transmission electron microscopy. Results The peritoneal membrane in normal subjects consisted of a monolayer of mesothelial cells on a basement membrane and a layer of connective tissue containing cells,blood vessels,and lymphatic vessels. Mesothelial cells were polygonal,often elongated,and had numerous microvilli on their luminal surface. There were lots of oval or roundish pinocytotic vesicles in the cytoplasm of the mesothelial cells. The peritoneal morphology of uremic nondialysis patients was similar to that of normal subjects. However,significant abnormalities of the peritoneal membrane were observed in PD patients,and the changes were found to be progressive. Microvilli were the first site of damage which involved microvilli shortening,a gradual reduction in their number,and,eventually,the total disappearance of microvilli. Mesothelial cells then detached from the basement membrane, disappearing completely in some cases. In the end,the peritoneal membrane consisted only of submesothelial connective tissue without any cells.Conclusions PD can modify peritoneal morphology and structure. The morphological change is progressive and may be one of the important causes of peritoneal failure. Peritoneal biopsies can provide lots of valuable information about the effects of PD. Studying the relationship between peritoneal structure and its function proved very useful for understanding the physiopathology of the peritoneum during PD.