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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

Structural alteration of the peritoneal membrane during PD. (a) Normal peritoneal tissue from a healthy donor stained with Haematoxylin-eosin (H&E) shows a preserved MCs monolayer that lines a compact zone of connective tissue (A). Peritoneal membrane from a PD patient stained with H&E shows the loss of the MCs monolayer and increased thickness of the compact zone (B). Magnification ×200. Staining of the peritoneal vessels with anti-CD31 antibody demonstrates an intense angiogenesis in peritoneal membrane from PD patient (C). Hyalinizing vasculopathy can be observed in the peritoneal tissue from PD patient (D). Immunohistochemical analysis of the peritoneal membrane from PD patient reveals the presence of fibroblast-like cells embedded in the fibrotic stroma expressing the mesothelial markers cytokeratins and calretinin (E) and (F). Magnification ×150. (b) Schematic representation of the progressive alterations of the peritoneal membrane in the time course of PD.
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fig1: Structural alteration of the peritoneal membrane during PD. (a) Normal peritoneal tissue from a healthy donor stained with Haematoxylin-eosin (H&E) shows a preserved MCs monolayer that lines a compact zone of connective tissue (A). Peritoneal membrane from a PD patient stained with H&E shows the loss of the MCs monolayer and increased thickness of the compact zone (B). Magnification ×200. Staining of the peritoneal vessels with anti-CD31 antibody demonstrates an intense angiogenesis in peritoneal membrane from PD patient (C). Hyalinizing vasculopathy can be observed in the peritoneal tissue from PD patient (D). Immunohistochemical analysis of the peritoneal membrane from PD patient reveals the presence of fibroblast-like cells embedded in the fibrotic stroma expressing the mesothelial markers cytokeratins and calretinin (E) and (F). Magnification ×150. (b) Schematic representation of the progressive alterations of the peritoneal membrane in the time course of PD.

Mentions: The bioincompatible nature of some PD fluids and episodes of bacterial and fungal infection are considered the main etiologic factors of peritoneal deterioration [2, 12, 19, 25, 33]. They induce acute and chronic inflammatory and reparative responses that initiate the structural alterations of the peritoneal membrane including loss of MCs monolayer, fibrosis, angiogenesis, and hyalinizing vasculopathy [30, 31, 34–36] (Figure 1). Such alterations are considered the major cause of ultrafiltration failure and loss of the dialytic capacity of the peritoneum [2, 19, 37, 38]. There is emerging evidence suggesting that the local injury induced by classical glucose-based PD fluids is mediated, at least in part, by the presence of GDPs and by the acidic pH. GDPs through the formation advanced glycation-end products (AGEs) may stimulate the production of extracellular matrix components (ECM) as well as the synthesis of profibrotic and angiogenic factors [2, 19]. Several studies have demonstrated the appearance of AGEs in the peritoneal effluents of PD patients, which correlated with the time on PD treatment. Biopsy studies have confirmed the accumulation of AGEs in the peritoneal tissues of PD patients. The intensity of AGEs accumulation is associated with fibrosis and ultrafiltration dysfunction [2, 19].


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

López-Cabrera M - Adv Med (2014)

Structural alteration of the peritoneal membrane during PD. (a) Normal peritoneal tissue from a healthy donor stained with Haematoxylin-eosin (H&E) shows a preserved MCs monolayer that lines a compact zone of connective tissue (A). Peritoneal membrane from a PD patient stained with H&E shows the loss of the MCs monolayer and increased thickness of the compact zone (B). Magnification ×200. Staining of the peritoneal vessels with anti-CD31 antibody demonstrates an intense angiogenesis in peritoneal membrane from PD patient (C). Hyalinizing vasculopathy can be observed in the peritoneal tissue from PD patient (D). Immunohistochemical analysis of the peritoneal membrane from PD patient reveals the presence of fibroblast-like cells embedded in the fibrotic stroma expressing the mesothelial markers cytokeratins and calretinin (E) and (F). Magnification ×150. (b) Schematic representation of the progressive alterations of the peritoneal membrane in the time course of PD.
© Copyright Policy
Related In: Results  -  Collection

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

fig1: Structural alteration of the peritoneal membrane during PD. (a) Normal peritoneal tissue from a healthy donor stained with Haematoxylin-eosin (H&E) shows a preserved MCs monolayer that lines a compact zone of connective tissue (A). Peritoneal membrane from a PD patient stained with H&E shows the loss of the MCs monolayer and increased thickness of the compact zone (B). Magnification ×200. Staining of the peritoneal vessels with anti-CD31 antibody demonstrates an intense angiogenesis in peritoneal membrane from PD patient (C). Hyalinizing vasculopathy can be observed in the peritoneal tissue from PD patient (D). Immunohistochemical analysis of the peritoneal membrane from PD patient reveals the presence of fibroblast-like cells embedded in the fibrotic stroma expressing the mesothelial markers cytokeratins and calretinin (E) and (F). Magnification ×150. (b) Schematic representation of the progressive alterations of the peritoneal membrane in the time course of PD.
Mentions: The bioincompatible nature of some PD fluids and episodes of bacterial and fungal infection are considered the main etiologic factors of peritoneal deterioration [2, 12, 19, 25, 33]. They induce acute and chronic inflammatory and reparative responses that initiate the structural alterations of the peritoneal membrane including loss of MCs monolayer, fibrosis, angiogenesis, and hyalinizing vasculopathy [30, 31, 34–36] (Figure 1). Such alterations are considered the major cause of ultrafiltration failure and loss of the dialytic capacity of the peritoneum [2, 19, 37, 38]. There is emerging evidence suggesting that the local injury induced by classical glucose-based PD fluids is mediated, at least in part, by the presence of GDPs and by the acidic pH. GDPs through the formation advanced glycation-end products (AGEs) may stimulate the production of extracellular matrix components (ECM) as well as the synthesis of profibrotic and angiogenic factors [2, 19]. Several studies have demonstrated the appearance of AGEs in the peritoneal effluents of PD patients, which correlated with the time on PD treatment. Biopsy studies have confirmed the accumulation of AGEs in the peritoneal tissues of PD patients. The intensity of AGEs accumulation is associated with fibrosis and ultrafiltration dysfunction [2, 19].

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