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Published on: July 19, 2018
Transition of mesothelial cell to fibroblast in peritoneal dialysis: EMT, stem cell or bystander?
Yu Liu1, Zheng Dong2, Hong Liu1
1Department of Nephrology, the Second Xiangya Hospital, Central South University, Changsha, Hunan, PR China; Department of Cellular Biology and Anatomy, Georgia Regents University and Charlie Norwood Veterans Affairs Medical Center, Augusta, Georgia, USA.
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.
Insights
Peritoneal dialysis can cause peritoneal fibrosis. This review questions the role of epithelial-mesenchymal transition (EMT) and explores mesothelial cells (MCs) as a potential source of myofibroblasts in fibrosis.
Area of Science:
- Nephrology
- Cell Biology
- Histology
Background:
- Long-term peritoneal dialysis (PD) is associated with peritoneal fibrosis, characterized by mesothelial cell (MC) loss and submesothelial thickening.
- The origin of myofibroblasts, key contributors to fibrosis, remains a critical question in peritoneal fibrosis research.
Purpose of the Study:
- To review the evidence for and against epithelial-mesenchymal transition (EMT) as the primary mechanism driving myofibroblast generation in PD-related peritoneal fibrosis.
- To discuss alternative sources of myofibroblasts, particularly the potential role of peritoneal mesothelial cells (MCs).
Main Methods:
- Literature review of clinical and experimental studies on peritoneal fibrosis and EMT.
- Analysis of recent findings from cell isolation and lineage-tracing experiments.
Main Results:
- While EMT has been a proposed mechanism for myofibroblast generation, recent studies cast doubt on its significance in organ fibrogenesis.
- Evidence suggests the existence of peritoneal progenitor cells capable of differentiating into myofibroblasts.
Conclusions:
- The role of EMT in peritoneal fibrosis requires re-evaluation.
- Peritoneal mesothelial cells (MCs) possess plasticity and may contribute to myofibroblast pools, warranting further investigation into their role in peritoneal fibrogenesis.
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