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

López-Cabrera M - Adv Med (2014)

Bottom Line: In parallel with these peritoneal alterations, mesothelial cells undergo an epithelial to mesenchymal transition (EMT), which has been associated with peritoneal deterioration.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.

View Article: PubMed Central - PubMed

Affiliation: Centro de Biología Molecular-Severo Ochoa, CSIC, UAM, Cantoblanco, C/Nicolás Cabrera 1, 28049 Madrid, Spain.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

Schematic illustration of the key events during MMT. Mesothelial to mesenchymal transition (MMT) occurs when mesothelial cells lose their epithelial-like characteristics, including dissolution of cell-cell junctions, that is, tight junctions, adherens junctions and desmosomes, and loss of apical-basolateral polarity, and acquire a mesenchymal phenotype, characterized by actin reorganization and stress fiber formation, migration, and invasion. The diagram shows four key steps essential for the completion of entire MMT, the most commonly used mesothelial and mesenchymal markers, and the molecules and signal transduction pathways that act either as inducer or modulator of the MMT process. See text for details.
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fig3: Schematic illustration of the key events during MMT. Mesothelial to mesenchymal transition (MMT) occurs when mesothelial cells lose their epithelial-like characteristics, including dissolution of cell-cell junctions, that is, tight junctions, adherens junctions and desmosomes, and loss of apical-basolateral polarity, and acquire a mesenchymal phenotype, characterized by actin reorganization and stress fiber formation, migration, and invasion. The diagram shows four key steps essential for the completion of entire MMT, the most commonly used mesothelial and mesenchymal markers, and the molecules and signal transduction pathways that act either as inducer or modulator of the MMT process. See text for details.

Mentions: MCs have a mesodermal origin and share characteristics with both epithelial cells and endothelial cells, which may undergo EMT and endothelial to mesenchymal transition (EndMT), respectively. Thus, recently several authors have proposed renaming the mesenchymal conversion of MCs, that takes place in different organs such as lung, liver, or peritoneum, with a more appropriate term: mesothelial to mesenchymal transition (MMT) [62, 82, 108–111]. MMT is a complex and step-wise process that requires alterations in cellular architecture and a deep molecular reprogramming with new biochemical instruction [19, 25, 58]. MMT starts with the dissociation of intercellular junctions, due to downregulation of intercellular adhesion molecules, and with the loss of microvilli and apical-basal polarity. Then, the cells adopt a front to back polarity and acquire α-SMA expression and increased migratory capacity. In the latest stages of MMT, the cells increase their capacity to degrade the basement membrane and to invade the fibrotic compact zone (Figure 3). During the end-stages of the myofibroblast conversion, the MCs are able to produce large amount of extracellular matrix components and to synthesize a wide range of inflammatory, profibrotic, and angiogenic factors that may contribute to the structural and functional deterioration of the peritoneal membrane [2, 19, 25, 58]. Other commonly used molecular markers for MMT include the downregulation of cytokeratins, Wilm's tumor protein-1 (WT1), and calretinin and up-regulation of N-cadherin, FSP-1, and transcription factor snail (Figure 3).


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

López-Cabrera M - Adv Med (2014)

Schematic illustration of the key events during MMT. Mesothelial to mesenchymal transition (MMT) occurs when mesothelial cells lose their epithelial-like characteristics, including dissolution of cell-cell junctions, that is, tight junctions, adherens junctions and desmosomes, and loss of apical-basolateral polarity, and acquire a mesenchymal phenotype, characterized by actin reorganization and stress fiber formation, migration, and invasion. The diagram shows four key steps essential for the completion of entire MMT, the most commonly used mesothelial and mesenchymal markers, and the molecules and signal transduction pathways that act either as inducer or modulator of the MMT process. See text for details.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4590954&req=5

fig3: Schematic illustration of the key events during MMT. Mesothelial to mesenchymal transition (MMT) occurs when mesothelial cells lose their epithelial-like characteristics, including dissolution of cell-cell junctions, that is, tight junctions, adherens junctions and desmosomes, and loss of apical-basolateral polarity, and acquire a mesenchymal phenotype, characterized by actin reorganization and stress fiber formation, migration, and invasion. The diagram shows four key steps essential for the completion of entire MMT, the most commonly used mesothelial and mesenchymal markers, and the molecules and signal transduction pathways that act either as inducer or modulator of the MMT process. See text for details.
Mentions: MCs have a mesodermal origin and share characteristics with both epithelial cells and endothelial cells, which may undergo EMT and endothelial to mesenchymal transition (EndMT), respectively. Thus, recently several authors have proposed renaming the mesenchymal conversion of MCs, that takes place in different organs such as lung, liver, or peritoneum, with a more appropriate term: mesothelial to mesenchymal transition (MMT) [62, 82, 108–111]. MMT is a complex and step-wise process that requires alterations in cellular architecture and a deep molecular reprogramming with new biochemical instruction [19, 25, 58]. MMT starts with the dissociation of intercellular junctions, due to downregulation of intercellular adhesion molecules, and with the loss of microvilli and apical-basal polarity. Then, the cells adopt a front to back polarity and acquire α-SMA expression and increased migratory capacity. In the latest stages of MMT, the cells increase their capacity to degrade the basement membrane and to invade the fibrotic compact zone (Figure 3). During the end-stages of the myofibroblast conversion, the MCs are able to produce large amount of extracellular matrix components and to synthesize a wide range of inflammatory, profibrotic, and angiogenic factors that may contribute to the structural and functional deterioration of the peritoneal membrane [2, 19, 25, 58]. Other commonly used molecular markers for MMT include the downregulation of cytokeratins, Wilm's tumor protein-1 (WT1), and calretinin and up-regulation of N-cadherin, FSP-1, and transcription factor snail (Figure 3).

Bottom Line: In parallel with these peritoneal alterations, mesothelial cells undergo an epithelial to mesenchymal transition (EMT), which has been associated with peritoneal deterioration.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.

View Article: PubMed Central - PubMed

Affiliation: Centro de Biología Molecular-Severo Ochoa, CSIC, UAM, Cantoblanco, C/Nicolás Cabrera 1, 28049 Madrid, Spain.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus