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

Abstract

BackgroundPeritoneal dialysis (PD) therapy is known to induce morphological and functional changes in the peritoneal membrane. Long-term exposure to conventional bio-incompatible dialysate and peritonitis is the main etiology of inflammation. Consequently, the peritoneal membrane undergoes structural changes, including angiogenesis, fibrosis, and hyalinizing vasculopathy, which ultimately results in technique failure. The epithelial-to-mesenchymal transition (EMT) of mesothelial cells (MCs) plays an important role during the above process; however, the clinical parameters associated with the EMT process of MCs remain to be explored.MethodsTo investigate the parameters impacting EMT during PD therapy, 53 clinical stable PD patients were enrolled. EMT assessments were conducted through human peritoneal MCs cultured from dialysate effluent with one consistent standard criterion (MC morphology and the expression of an epithelial marker, cytokeratin 18). The factors potentially associated with EMT were analyzed using logistic regression analysis. Primary MCs derived from the omentum were isolated for the in vitro study.ResultsForty-seven percent of the patients presented with EMT, 28% with non-EMT, and 15% with a mixed presentation. Logistic regression analysis showed that patients who received persistent PD therapy (dwelling time of 24 h/day) had significantly higher EMT tendency. These results were consistent in vitro.ConclusionsDwelling time had a significant effect on the occurrence of EMT on MCs.

Mesothelial cells in tissue repair and fibrosis

“…Other cell sources that may be used for mesothelial repair include bone marrow derived cells ( Sekiguchi et al, 2012 ), adipose-derived stem cells ( Kim et al, 2014 ), and mesenchymal stem cells ( Wang et al, 2012 ; Ueno et al, 2013 ). Alternative therapeutic strategies being investigated to reduce mesothelial cell-mediated inflammation and prevent peritoneal fibrosis include targeting TGFβ1-mediated mechanisms ( Hung et al, 2001 , 2003 ; Yung et al, 2001 ; Margetts et al, 2002a ; Fang et al, 2006 ; Tomino, 2012 ; Jang et al, 2013 ), reducing mesothelial cell production of fibronectin ( Tong et al, 2012 ; Zhang et al, 2014 ) developing a more bio compatible PD solution ( Bajo et al, 2000 ; Le Poole et al, 2005 ), altering PD daily dwelling time ( Lee et al, 2014 ), and stimulating fibrinolytic agents ( Haslinger et al, 2003 ).…”

Molecular hydrogen regulates PTEN‐AKT‐mTOR signaling via ROS to alleviate peritoneal dialysis‐related peritoneal fibrosis

“…During the process of peritoneal fibrosis, key fibrotic factors work through their membrane receptors and specific downstream intracellular signal cascades to trigger the transcription factors that activate the transcription of the cell matrix genes. These signal transduction cascades include transforming growth factor‐β (TGF‐β)/Smad and mitogen‐activated protein kinase (MAPK) signal pathways and a variety of noncoding RNAs (ncRNAs) . Given the prevalence and severity of peritoneal fibrosis, unfortunately, there are not enough specific and effective anti‐fibrosis therapies for this disease.…”

“…These signal transduction cascades include transforming growth factor-β (TGF-β)/Smad and mitogen-activated protein kinase (MAPK) signal pathways and a variety of noncoding RNAs (ncRNAs). 4,5 Given the prevalence and severity of peritoneal fibrosis, unfortunately, there are not enough specific and effective anti-fibrosis therapies for this disease.…”

Vitamin D Can Ameliorate Chlorhexidine Gluconate-Induced Peritoneal Fibrosis and Functional Deterioration through the Inhibition of Epithelial-to-Mesenchymal Transition of Mesothelial Cells

“…EMT plays a role in PD-related peritoneal membrane morphological and functional alterations [ 19 , 20 ]. The EMT begins with the downregulation of selected adhesion molecules, such as E-cadherin, and dissociation of the intercellular junctions of MCs.…”