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.

scholarly journals Methylglyoxal Induced Basophilic Spindle Cells with Podoplanin at the Surface of Peritoneum in Rat Peritoneal Dialysis Model

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Ichiro Hirahara ◽  
Hideki Sato ◽  
Toshimi Imai ◽  
Akira Onishi ◽  
Yoshiyuki Morishita ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Structural Changes ◽  
Epithelial To Mesenchymal Transition ◽  
Degradation Products ◽  
Smooth Muscle Actin ◽  
Functional Decline ◽  
Intraperitoneal Administration ◽  
Mesothelial Cells ◽  
Mesenchymal Transition ◽  
Spindle Cells

Peritoneal dialysis (PD) is a common treatment for patients with reduced or absent renal function. Long-term PD leads to peritoneal injury with structural changes and functional decline. At worst, peritoneal injury leads to encapsulating peritoneal sclerosis (EPS), which is a serious complication of PD. In order to carry out PD safely, it is important to define the mechanism of progression of peritoneal injury and EPS. We prepared rat models of peritoneal injury by intraperitoneal administration of glucose degradation products, such as methylglyoxal (MGO) or formaldehyde (FA), chlorhexidine gluconate (CG), and talc. In rats treated with MGO, peritoneal fibrous thickening with the appearance of basophilic spindle cells with podoplanin, cytokeratin, andα-smooth muscle actin at the surface of the peritoneum was observed. These cells may have been derived from mesothelial cells by epithelial-to-mesenchymal transition. In FA- or CG-treated rats, the peritoneum was thickened, and mesothelial cells were absent at the surface of the peritoneum. The CG- or MGO-treated rats presented with a so-called abdominal cocoon. In the talc-treated rats, extensive peritoneal adhesion and peritoneal thickening were observed. MGO-induced peritoneal injury model may reflect human histopathology and be suitable to analyze the mechanism of progression of peritoneal injury and EPS.

scholarly journals Mesenchymal Conversion of Mesothelial Cells Is a Key Event in the Pathophysiology of the Peritoneum during Peritoneal Dialysis

2014 ◽  
Vol 2014 ◽  
pp. 1-17 ◽  
Author(s):  
Manuel López-Cabrera
Keyword(s):  
Peritoneal Dialysis ◽  
Epithelial To Mesenchymal Transition ◽  
Degradation Products ◽  
Therapeutic Option ◽  
Functional Decline ◽  
Mesothelial Cells ◽  
Peritoneal Membrane ◽  
Pharmacological Agents ◽  
Membrane Function ◽  
Mesenchymal Transition

Peritoneal dialysis (PD) is a therapeutic option for the treatment of end-stage renal disease and is based on the use of the peritoneum as a semipermeable membrane for the exchange of toxic solutes and water. Long-term exposure of the peritoneal membrane to hyperosmotic PD fluids causes inflammation, loss of the mesothelial cells monolayer, fibrosis, vasculopathy, and angiogenesis, which may lead to peritoneal functional decline. Peritonitis may further exacerbate the injury of the peritoneal membrane. In parallel with these peritoneal alterations, mesothelial cells undergo an epithelial to mesenchymal transition (EMT), which has been associated with peritoneal deterioration. Factors contributing to the bioincompatibility of classical PD fluids include the high content of glucose/glucose degradation products (GDPs) and their acidic pH. New generation low-GDPs-neutral pH fluids have improved biocompatibility resulting in better preservation of the peritoneum. However, standard glucose-based fluids are still needed, as biocompatible solutions are expensive for many potential users. An alternative approach to preserve the peritoneal membrane, complementary to the efforts to improve fluid biocompatibility, is the use of pharmacological agents protecting the mesothelium. This paper provides a comprehensive review of recent advances that point to the EMT of mesothelial cells as a potential therapeutic target to preserve membrane function.

scholarly journals Shorter daily dwelling time in peritoneal dialysis attenuates the epithelial-to-mesenchymal transition of mesothelial cells

2014 ◽  
Vol 15 (1) ◽  
Author(s):  
Yi-Che Lee ◽  
Yau-Sheng Tsai ◽  
Shih-Yuan Hung ◽  
Tsun-Mei Lin ◽  
Sheng-Hsiang Lin ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Epithelial To Mesenchymal Transition ◽  
Mesothelial Cells ◽  
Mesenchymal Transition ◽  
Dwelling Time

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.

Peritoneal Dialysis and Epithelial-to-Mesenchymal Transition of Mesothelial Cells

2003 ◽  
Vol 348 (5) ◽  
pp. 403-413 ◽  
Author(s):  
María Yáñez-Mó ◽  
Enrique Lara-Pezzi ◽  
Rafael Selgas ◽  
Marta Ramírez-Huesca ◽  
Carmen Domínguez-Jiménez ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Epithelial To Mesenchymal Transition ◽  
Mesothelial Cells ◽  
Mesenchymal Transition

Ex Vivo Analysis of Dialysis Effluent-Derived Mesothelial Cells as an Approach to Unveiling the Mechanism of Peritoneal Membrane Failure

2006 ◽  
Vol 26 (1) ◽  
pp. 26-34 ◽  
Author(s):  
Manuel López-Cabrera ◽  
Abelardo Aguilera ◽  
Luiz S. Aroeira ◽  
Marta Ramírez-Huesca ◽  
M. Luisa Pérez-Lozano ◽  
...  
Keyword(s):  
Epithelial To Mesenchymal Transition ◽  
Ex Vivo ◽  
Functional Decline ◽  
Mesothelial Cells ◽  
Therapeutic Interventions ◽  
Peritoneal Membrane ◽  
Peritoneal Fibrosis ◽  
Stromal Fibroblasts ◽  
Mesenchymal Transition ◽  
Ultrafiltration Failure

During peritoneal dialysis (PD), the peritoneum is exposed to bioincompatible dialysis fluids, which causes progressive fibrosis and angiogenesis and, ultimately, ultrafiltration failure. In addition, repeated episodes of peritonitis or hemoperitoneum may accelerate all these processes. Fibrosis has been classically considered the main cause of peritoneal membrane functional decline. However, in parallel with fibrosis, the peritoneum also displays increases in capillary number (angiogenesis) and vasculopathy in response to PD. Nowadays, there is emerging evidence pointing to peritoneal microvasculature as the main factor responsible for increased solute transport and ultrafiltration failure. However, the pathophysiologic mechanism(s) involved in starting and maintaining peritoneal fibrosis and angiogenesis remain(s) elusive. Peritoneal stromal fibroblasts have been considered (for many years) the cell type mainly involved in structural and functional alterations of the peritoneum; whereas mesothelial cells have been considered mere victims of peritoneal injury caused by PD. Recently, ex vivo cultures of effluent-derived mesothelial cells, in conjunction with immunohistochemical analysis of peritoneal biopsies from PD patients, have identified mesothelial cells as culprits, at least in part, in peritoneal membrane deterioration. This review discusses recent findings that suggest new peritoneal myofibroblastic cells may arise from local conversion of mesothelial cells by epithelial-to-mesenchymal transition during the repair responses that take place in PD. The transdifferentiated mesothelial cells may retain a permanent mesenchymal state, as long as initiating stimuli persist, and contribute to PD-induced fibrosis and angiogenesis, and hence to membrane failure. Future therapeutic interventions could be designated in order to prevent or reverse epithelial-to-mesenchymal transition of mesothelial cells, or its pernicious effects.

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