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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

Multiple origins of myofibroblasts have been proposed in tissue fibrosis. Myofibroblasts may derive from at least five different sources through various mechanisms: phenotypic activation from interstitial fibroblasts; differentiation from vascular pericytes; recruitment from circulating fibrocytes; capillary endothelial-mesenchymal transition (EndMT); and epithelial-mesenchymal transition (EMT). The relative contribution of each source to the myofibroblast pool in peritoneal fibrosis still requires further studies.
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fig2: Multiple origins of myofibroblasts have been proposed in tissue fibrosis. Myofibroblasts may derive from at least five different sources through various mechanisms: phenotypic activation from interstitial fibroblasts; differentiation from vascular pericytes; recruitment from circulating fibrocytes; capillary endothelial-mesenchymal transition (EndMT); and epithelial-mesenchymal transition (EMT). The relative contribution of each source to the myofibroblast pool in peritoneal fibrosis still requires further studies.

Mentions: The origin of myofibroblasts is still an open question and a matter of intense debate [76–81], but it is generally accepted that these fibroblasts constitute a heterogeneous population that may derive from multiple sources (Figure 2). There is emerging evidence that the origin of myofibroblasts may vary between different organs and within different areas of individual organs. These observations may suggest that tissue- and organ-specific microenvironments dictate the different proportions of myofibroblasts subpopulations [76, 77, 82–87]. The activation of resident fibroblasts has classically been considered the main origin of myofibroblasts in most fibrotic pathologies [70–73, 83, 86]. Other studies have pointed to cells recruited from the bone marrow (fibrocytes) as an important source of myofibroblasts in several fibrotic disorders [76, 87–90]. In addition, it has been shown that the local conversion of epithelial cells and endothelial cells may also contribute to the accumulation of myofibroblasts in some reparative and fibrotic diseases. The conversion into myofibroblasts by these cells is achieved through two closely related processes termed epithelial to mesenchymal transition (EMT) and endothelial to mesenchymal transition (EndMT), respectively [86, 90–95]. More recently it has been suggested that vessel-associated pericytes may also transdifferentiate into myofibroblasts [77, 96] (Figure 2).


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

López-Cabrera M - Adv Med (2014)

Multiple origins of myofibroblasts have been proposed in tissue fibrosis. Myofibroblasts may derive from at least five different sources through various mechanisms: phenotypic activation from interstitial fibroblasts; differentiation from vascular pericytes; recruitment from circulating fibrocytes; capillary endothelial-mesenchymal transition (EndMT); and epithelial-mesenchymal transition (EMT). The relative contribution of each source to the myofibroblast pool in peritoneal fibrosis still requires further studies.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig2: Multiple origins of myofibroblasts have been proposed in tissue fibrosis. Myofibroblasts may derive from at least five different sources through various mechanisms: phenotypic activation from interstitial fibroblasts; differentiation from vascular pericytes; recruitment from circulating fibrocytes; capillary endothelial-mesenchymal transition (EndMT); and epithelial-mesenchymal transition (EMT). The relative contribution of each source to the myofibroblast pool in peritoneal fibrosis still requires further studies.
Mentions: The origin of myofibroblasts is still an open question and a matter of intense debate [76–81], but it is generally accepted that these fibroblasts constitute a heterogeneous population that may derive from multiple sources (Figure 2). There is emerging evidence that the origin of myofibroblasts may vary between different organs and within different areas of individual organs. These observations may suggest that tissue- and organ-specific microenvironments dictate the different proportions of myofibroblasts subpopulations [76, 77, 82–87]. The activation of resident fibroblasts has classically been considered the main origin of myofibroblasts in most fibrotic pathologies [70–73, 83, 86]. Other studies have pointed to cells recruited from the bone marrow (fibrocytes) as an important source of myofibroblasts in several fibrotic disorders [76, 87–90]. In addition, it has been shown that the local conversion of epithelial cells and endothelial cells may also contribute to the accumulation of myofibroblasts in some reparative and fibrotic diseases. The conversion into myofibroblasts by these cells is achieved through two closely related processes termed epithelial to mesenchymal transition (EMT) and endothelial to mesenchymal transition (EndMT), respectively [86, 90–95]. More recently it has been suggested that vessel-associated pericytes may also transdifferentiate into myofibroblasts [77, 96] (Figure 2).

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