Transition of Mesothelial Cell to Fibroblast in Peritoneal Dialysis: EMT, Stem Cell or Bystander?

Abstract

Long-term peritoneal dialysis (PD) can lead to fibrotic changes in the peritoneum, characterized by loss of mesothelial cells (MCs) and thickening of the submesothelial area with an accumulation of collagen and myofibroblasts. The origin of myofibroblasts is a central question in peritoneal fibrosis that remains unanswered at present. Numerous clinical and experimental studies have suggested that MCs, through epithelial-mesenchymal transition (EMT), contribute to the pool of peritoneal myofibroblasts. However, recent work has placed significant doubts on the paradigm of EMT in organ fibrogenesis (in the kidney particularly), highlighting the need to reconsider the role of EMT in the generation of myofibroblasts in peritoneal fibrosis. In particular, selective cell isolation and lineage-tracing experiments have suggested the existence of progenitor cells in the peritoneum, which are able to switch to fibroblast-like cells when stimulated by the local environment. These findings highlight the plastic nature of MCs and its contribution to peritoneal fibrogenesis. In this review, we summarize the key findings and caveats of EMT in organ fibrogenesis, with a focus on PD-related peritoneal fibrosis, and discuss the potential of peritoneal MCs as a source of myofibroblasts.

Tanshinone IIA mitigates peritoneal fibrosis by inhibiting EMT via regulation of TGF-β/smad pathway

“…EMT is a highly regulated process that has a vital role in embryonic development, tumor formation and fibrosis in some chronic inflammatory diseases [3,4]. Peritoneal mesothelial cell EMT is one of the key factors responsible for gradual decreases in peritoneal functions in peritoneal dialysis patients [3,4]. TGF-β1 is an important fibrosis-promoting factor in several tissues and organs, including peritoneal tissue; its role is to phosphorylate the signaling protein smad2 /3 [17].…”

“…However, recent studies have found that the long-term stimulation by nonbiocompatible peritoneal dialysis solution can lead to the EMT of peritoneal mesothelial cells [2,3,16]. EMT is a highly regulated process that has a vital role in embryonic development, tumor formation and fibrosis in some chronic inflammatory diseases [3,4]. Peritoneal mesothelial cell EMT is one of the key factors responsible for gradual decreases in peritoneal functions in peritoneal dialysis patients [3,4].…”

“…Multiple mechanisms contribute to the incidence and progression of the disease. These include fibrosis-promoting factor, oxidative stress and peritoneal EMT of mesothelial cells [3,4]. However, EMT is the main mechanism involved in peritoneal fibrosis [4].…”

“…Factors such as peritoneal dialysis fluid biocompatibility, peritonitis, and cytokines are implicated in the etiology of peritoneal fibrosis [3,4]. Multiple mechanisms contribute to the incidence and progression of the disease.…”

“…Peritoneal fibrosis is characterized by absence of peritoneal mesothelial cell layer and increase in mesenchymal layer [3,4]. Factors such as peritoneal dialysis fluid biocompatibility, peritonitis, and cytokines are implicated in the etiology of peritoneal fibrosis [3,4].…”