scholarly journals Effect of lactate as a peritoneal dialysis fluid buffer on rat peritoneal mesothelial cells

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Chieko Higuchi ◽  
Junko Kuriyama ◽  
Hiroshi Sakura
Keyword(s):  
Peritoneal Dialysis ◽  
Growth Factor ◽  
Mesothelial Cells ◽  
Matrix Metalloproteinase 2 ◽  
Dialysis Fluid ◽  
Mesenchymal Transition ◽  
Peritoneal Mesothelial Cells ◽  
Peritoneal Dialysis Fluid ◽  
E Cadherin

Abstract Background Neutral, low-glucose degradation product (GDP) peritoneal dialysis fluid (PDF) is less damaging to the peritoneum than conventional PDF but is still insufficient for biocompatibility. One remaining issue is the problem of buffering. Methods Using cultured rat peritoneal mesothelial cells (PMCs), the present study examined the difference between the effects of neutral low-GDP lactate PDF and neutral low-GDP bicarbonate/lactate PDF on cells. The effects of lactate stimulation on these cells were also examined. Results Lactate PDF enhanced mRNA expressions of α-smooth muscle actin (αSMA) and type 1 and type 3 collagens and lowered expression of e-cadherin mRNA in PMCs compared to bicarbonate/lactate PDF. Lactate stimulation increased mRNA expressions of αSMA, matrix metalloproteinase 2 (MMP2), and basic fibroblast growth factor (bFGF) and suppressed e-cadherin mRNA expression. Transforming growth factor (TGF)-β1 and TGF-β2 and collagen type 1 and 3 mRNA expressions were also enhanced by lactate stimulation. Conclusions These results suggest that lactate as a PDF buffer may act on PMCs to promote epithelial-mesenchymal transition (EMT) and production of TGF-β, bFGF, and collagen.

scholarly journals Influence of Bicarbonate/Low-GDP Peritoneal Dialysis Fluid (Bicavera) onin VitroandEx VivoEpithelial-to-Mesenchymal Transition of Mesothelial Cells

2012 ◽  
Vol 32 (3) ◽  
pp. 292-304 ◽  
Author(s):  
Antonio Fernández–Perpén ◽  
María Luisa Pérez–Lozano ◽  
María–Auxiliadora Bajo ◽  
Patricia Albar–Vizcaino ◽  
Pilar Sandoval Correa ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Growth Factor ◽  
Ex Vivo ◽  
Mesothelial Cells ◽  
Interleukin 8 ◽  
Mesenchymal Transition ◽  
Standard Solution ◽  
The Impact ◽  
E Cadherin

BackgroundPeritoneal membrane damage induced by peritoneal dialysis (PD) is largely associated with epithelial-to-mesenchymal transition (EMT) of mesothelial cells (MCs), which is believed to be a result mainly of the glucose degradation products (GDPs) present in PD solutions.ObjectivesThis study investigated the impact of bicarbonate-buffered, low-GDP PD solution (BicaVera: Fresenius Medical Care, Bad Homburg, Germany) on EMT of MCs in vitro and ex vivo.Methods: studiesOmentum-derived MCs were incubated with lactate-buffered standard PD fluid or Bica-Vera fluid diluted 1:1 with culture medium. Ex vivo studies: From 31 patients randomly distributed to either standard or BicaVera solution and followed for 24 months, effluents were collected every 6 months for determination of EMT markers in effluent MCs.ResultsCulturing of MCs with standard fluid in vitro resulted in morphology change to a non-epithelioid shape, with downregulation of E-cadherin (indicative of EMT) and strong induction of vascular endothelial growth factor (VEGF) expression. By contrast, in vitro exposure of MCs to bicarbonate/low-GDP solution had less impact on both EMT parameters. Ex vivo studies partially confirmed the foregoing results. The BicaVera group, with a higher prevalence of the non-epithelioid MC phenotype at baseline (for unknown reasons), showed a clear and significant trend to gain and maintain an epithelioid phenotype at medium- and longer-term and to show fewer fibrogenic characteristics. By contrast, the standard solution group demonstrated a progressive and significantly higher presence of the non-epithelioid phenotype. Compared with effluent MCs having an epithelioid phenotype, MCs with non-epithelioid morphology showed significantly lower levels of E-cadherin and greater levels of fibronectin and VEGF. In comparing the BicaVera and standard solution groups, MCs from the standard solution group showed significantly higher secretion of interleukin 8 and lower secretion of collagen I, but no differences in the levels of other EMT-associated molecules, including fibronectin, VEGF, E-cadherin, and transforming growth factor β1. Peritonitis incidence was similar in both groups. Functionally, the use of BicaVera fluid was associated with higher transport of small molecules and lower ultrafiltration capacity.ConclusionsEffluent MCs grown ex vivo from patients treated with bicarbonate/low-GDP BicaVera fluid showed a trend to acquire an epithelial phenotype, with lower production of proinflammatory cytokines and chemokines (such as interleukin 8) than was seen with MCs from patients treated with a lactate-buffered standard PD solution.

Impairment of MCP-1 Expression in Mesothelial Cells Exposed to Peritoneal Dialysis Fluid by Osmotic Stress and Acidic Stress

2011 ◽  
Vol 31 (1) ◽  
pp. 80-89 ◽  
Author(s):  
Ryouji Ogata ◽  
Nobuhiko Hiramatsu ◽  
Kunihiro Hayakawa ◽  
Shotaro Nakajima ◽  
Jian Yao ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Osmotic Stress ◽  
Map Kinase ◽  
Mesothelial Cells ◽  
P38 Map Kinase ◽  
Low Ph ◽  
Acidic Stress ◽  
Dialysis Fluid ◽  
Map Kinase Phosphatase ◽  
Peritoneal Dialysis Fluid

BackgroundBacterial peritonitis is one of the most frequent complications in patients on peritoneal dialysis. In the present study, we investigated effects of peritoneal dialysis fluid (PDF) on mesothelial cell recruitment of macrophages, focusing especially on unphysiological properties of PDF.MethodsHuman and murine mesothelial cells were exposed to PDF or individual properties of PDF (low pH, high glucose concentration, hyperosmolality, high lactate concentration) in vitro and in vivo, treated with inflammatory stimuli, and subjected to analyses of monocyte chemo-attractant protein-1 (MCP-1), nuclear factor-κB (NF-κB), mitogen-activated protein (MAP) kinases, and MAP kinase phosphatase-1 (MKP-1).ResultsWe found that intraperitoneal administration of PDF suppressed expression of MCP-1 and infiltration of mononuclear cells in the peritoneum of mice following injection with lipopolysaccharide. Among the unphysiological properties of PDF, low pH and hyperosmolality caused blunted induction of MCP-1 in cytokine-stimulated mesothelial cells. The attenuated response was ascribed to suppression of NF-κB by low pH and inhibition of p38 MAP kinase by hyperosmolality. Furthermore, the attenuated phosphorylation of p38 MAP kinase by osmotic stress was associated with induction of MKP-1.ConclusionThese results suggest a possibility that mesothelial cells exposed to PDF exhibit attenuated MCP-1 expression and consequent impairment of macrophage recruitment through dual mechanisms, that is, inhibition of NF-κB by acidic stress and blunted activation of p38 MAP kinase by osmotic stress. In patients on peritoneal dialysis, blunted expression of chemokines may lead to perturbation of bacterial clearance by macrophages in the peritoneal cavity.

scholarly journals Effluent Tenascin-C Levels Reflect Peritoneal Deterioration in Peritoneal Dialysis: MAJOR IN PD Study

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Ichiro Hirahara ◽  
Eiji Kusano ◽  
Toshimi Imai ◽  
Yoshiyuki Morishita ◽  
Makoto Inoue ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Structural Changes ◽  
Epithelial To Mesenchymal Transition ◽  
Functional Decline ◽  
Major Complication ◽  
Mesothelial Cells ◽  
Matrix Metalloproteinase 2 ◽  
Mesenchymal Transition ◽  
Tenascin C ◽  
Stage Renal Disease

Peritoneal deterioration causing structural changes and functional decline is a major complication of peritoneal dialysis (PD). The aim of this study was to explore effluent biomarkers reflecting peritoneal deterioration. In an animal study, rats were intraperitoneally administered with PD fluids adding 20 mM methylglyoxal (MGO) or 20 mM formaldehyde (FA) every day for 21 days. In the MGO-treated rats, tenascin-C (TN-C) levels in the peritoneal effluents were remarkably high and a cluster of TN-C-positive mesothelial cells with epithelial-to-mesenchymal transition- (EMT-) like change excessively proliferated at the peritoneal surface, but not in the FA-treated rats. Effluent matrix metalloproteinase-2 (MMP-2) levels increased in both the MGO- and FA-treated rats. In a clinical study at 18 centers between 2006 and 2013, effluent TN-C and MMP-2 levels were quantified in 182 PD patients with end-stage renal disease. Peritoneal function was estimated using the peritoneal equilibration test (PET). From the PET results, the D/P Cr ratio was correlated with effluent levels of TN-C (ρ= 0.57,p<0.001) and MMP-2 (ρ= 0.73,p<0.001). We suggest that TN-C in the effluents may be a diagnostic marker for peritoneal deterioration with EMT-like change in mesothelial cells in PD.

Peritoneal Dialysis Fluid Induces P38-Dependent Inflammation in Human Mesothelial Cells

2011 ◽  
Vol 31 (3) ◽  
pp. 332-339 ◽  
Author(s):  
Andrea Riesenhuber ◽  
Klaus Kratochwill ◽  
Thorsten O. Bender ◽  
Regina Vargha ◽  
David C. Kasper ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Stress Response ◽  
Stress Responses ◽  
Mesothelial Cells ◽  
Hsp70 Expression ◽  
Peritoneal Mesothelial Cells ◽  
P38 Inhibitor ◽  
Peritoneal Dialysis Fluid ◽  
Human Peritoneal Mesothelial Cells ◽  
Ldh Release

BackgroundNoninfectious upregulation of proinflammatory pathways in mesothelial cells may represent an integral part of their stress response upon exposure to peritoneal dialysis fluids (PDF).ObjectiveThe aim of this study was to evaluate the role of the stress-inducible mitogen-activated protein kinase (MAPK) p38 in regulation of inflammatory and stress responses in mesothelial cells following in vitro exposure to PDF.Materials and MethodsHuman peritoneal mesothelial cells were exposed to Dianeal PD4 or Physioneal (Baxter AG, Vienna, Austria) containing 1.36% glucose and then allowed to recover. Phosphorylation of p38, induction of heat shock protein-70 (HSP70), release of lactate dehydrogenase (LDH), secretion of interleukin (IL)-8, gene transcription, and mRNA stability were assessed with and without the MAPK p38 inhibitor SB203580.ResultsExposure to Dianeal resulted in phosphorylation of p38 within 30 minutes (309% of control, p < 0.05) and increased IL-8 release (370% of control, p < 0.05), HSP70 expression (151% of control, p < 0.05), and LDH release (180% of control, p < 0.05). Exposure to Physioneal resulted in attenuated changes in IL-8, HSP70, and LDH. Addition of the p38 inhibitor SB203580 to Dianeal resulted in dampened IL-8 release (-55%; p < 0.05) and basal HSP70 expression, and unchanged LDH release. Effects of p38 on IL-8 were at transcriptional, posttranscriptional, and translational levels.ConclusionThese data confirm concordant p38-dependent upregulation of IL-8 and HSP70 following exposure to bioincompatible PDF. The MAPK p38 pathway therefore links proinflammatory processes and the cellular stress response in human peritoneal mesothelial cells.

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