Peritoneal dialysis (PD) is a treatment for end-stage renal disease in which the blood-vessel-rich abdominal cavity lining, the peritoneum, is used essentially as an artificial kidney. Following the delivery of dialysis solution into the abdomen, ultrafiltration and diffusion take place across the peritoneal membrane to clean waste from the blood. However, continuous exposure to dialysis solutions, as well as episodes of peritoneum infection (peritonitis) and bleeding (hemoperitoneum), may induce peritoneal cell abnormalities and eventually lead to reduced ultrafiltration activity. These alterations are reminiscent of an epithelial-mesenchymal transition (EMT), a complex stepwise transformation of cells that takes place during embryonic development, and is also seen in disease states such as tumorigenesis, chronic inflammation, and fibrosis.
Aim and results
This study analyzes the signaling pathways that underlie the EMT of peritoneal mesothelial cells (MCs). The authors demonstrate that inflammatory cytokines, as well as peritoneal effluent from PD patients, induce EMT-like changes in primary MCs from human peritoneum. They also show that an ERK/NF-κB/Snail1 activation pathway regulates the establishment of an EMT in these cells. Interestingly, blockade of ERK and NF-κB activation induces the reversal of EMT in MCs collected from the peritoneal effluent of patients undergoing PD.
Implications and future directions
PD provides more advantages to the patient than hemodialysis, the traditional treatment for kidney failure, and is therefore increasingly used in the clinic. However, patients frequently discontinue PD owing to a loss of peritoneal ultrafiltration. One of the key events preceding this loss in filtration ability is EMT in the peritoneum. Studying the signaling pathways underlying EMT will facilitate development of specific pharmacological inhibitors to counteract and/or reverse the changes that lead to peritoneal fibrosis. Additionally, this information may help us to understand the other disease processes in which EMT takes place.