Peritoneal fibrosis and epigenetic modulation

Abstract

Peritoneal dialysis (PD) is an effective treatment for patients with end-stage renal disease. However, peritoneal fibrosis (PF) is a common complication that ultimately leads to ultrafiltration failure and discontinuation of PD after long-term PD therapy. There is currently no effective therapy to prevent or delay this pathologic process. Recent studies have reported epigenetic modifications involved in PF, and accumulating evidence suggests that epigenetic therapies may have the potential to prevent and treat PF clinically. The major epigenetic modifications in PF include DNA methylation, histone modification, and noncoding RNAs. The mechanisms of epigenetic regulation in PF are complex, predominantly involving modification of signaling molecules, transcriptional factors, and genes. This review will describe the mechanisms of epigenetic modulation in PF and discuss the possibility of targeting them to prevent and treat this complication.

Nintedanib attenuates peritoneal fibrosis by inhibiting mesothelial‐to‐mesenchymal transition, inflammation and angiogenesis

“…Increasing evidence indicates that peritoneal mesothelial‐to‐mesenchymal transition (MMT) is an early mechanism of peritoneal fibrosis. MMT is featured by the disruption of intercellular junctions and conversion of mesothelial cells to a mesenchymal phenotype 4,5 . These transformed mesothelial cells can secrete profibrotic and angiogenetic cytokines that prompt cells to produce excessive amounts of extracellular matrix (ECM) components, inducing vascularization and mononuclear cell infiltration 4,5 .…”

“…MMT is featured by the disruption of intercellular junctions and conversion of mesothelial cells to a mesenchymal phenotype 4,5 . These transformed mesothelial cells can secrete profibrotic and angiogenetic cytokines that prompt cells to produce excessive amounts of extracellular matrix (ECM) components, inducing vascularization and mononuclear cell infiltration 4,5 . Similar to the epithelial‐mesenchymal transition (EMT) in other tissues, MMT results from growth factor—activation of multiple signalling pathways and transcription factors.…”

Blocking core fucosylation of epidermal growth factor (EGF) receptor prevents peritoneal fibrosis progression

“…However, long-term PD treatment will result in peritoneal fibrosis, a frequent complication due to exposure to glucose peritoneal dialysate [ 3 , 4 ]. Peritoneal fibrosis may affect the function of the peritoneal membrane and ultimately lead to ultrafiltration failure and discontinuation of PD [ 5 , 6 ]. Unfortunately, the mechanism of peritoneal fibrosis is not fully elucidated [ 7–9 ], and there are few effective methods available to treat peritoneal fibrosis; therefore, targets to prevent peritoneal fibrosis are urgently required.…”

Mechanisms of Peritoneal Mesothelial Cells in Peritoneal Adhesion

“…PMCs have epithelial and mesenchymal features and can transform under physiological and pathological conditions [ 6 ]. The peritoneum is a naturally semipermeable membrane under physiological conditions [ 31 , 32 , 33 ], but after repeated peritoneal dialysis, PMCs undergo mesothelial–mesenchymal transformation (MMT), which can lead to peritoneal fibrosis [ 34 , 35 , 36 , 37 ]. In addition, PMCs can capture bacteria, chemical molecules, and other substances to play a protective barrier role [ 21 ].…”