BMP-7 blocks mesenchymal conversion of mesothelial cells and prevents peritoneal damage induced by dialysis fluid exposure

Abstract

Data point to a balance between BMP-7 and TGF-beta1 in the control of EMT and indicate that blockade of EMT may be a therapeutic approach to ameliorate peritoneal membrane damage during PD.

Blocking TGF-β1 Protects the Peritoneal Membrane from Dialysate-Induced Damage

“…We have previously shown that in response to PD, the pathologic fibroblasts may originate from resident fibroblasts and from the mesothelium via MMT. 11,12,39,46 Herein, we provide evidence for the first time that peritoneal FSP-1 ϩ fibroblasts may also derive from bone-marrow-derived circulating cells (CD45ϩ) and from the local conversion of endothelial cells (CD31ϩ) via EnMT. The percentage of mesothelial-cell-derived FSP-1 ϩ fibroblasts, 37%, in the injured peritoneum is in agreement with that found in renal fibrosis, in which approximately 36% come from local conversion of tubular epithelial cells via epithelialto-mesenchymal transition.…”

“…39,46 In the peritoneum from control saline-treated mice, there was no expression of FSP-1. By contrast, FSP-1 ϩ fibroblasts were present in the submesothelial compact region of mice treated with PD fluid ( Figure 5, A and B).…”

The monocyte chemoattractant protein-1 (MCP-1)/CCR2 system is involved in peritoneal dialysis-related epithelial–mesenchymal transition of peritoneal mesothelial cells

“…2 In addition, TGF-b1 has been shown to be a key cytokine involved in the process of EMT. 26,27 In this study, we showed for the first time that the MCP-1/CCR2 system was directly involved in PD-related EMT of PMCs and ECM accumulation. Moreover, we demonstrated that these effects of the MCP-1/CCR2 system were mediated, at least in part, by TGF-b1.…”

“…30 A number of recent studies have demonstrated that PMCs also undergo EMT during PD, leading to PF. 4,26,27 In the past, resident peritoneal fibroblasts and infiltrating inflammatory cells were considered to be responsible for PF, 6 but Yanez-Mo et al 4 were the first to show that PMCs underwent a transition from an epithelial phenotype to a mesenchymal phenotype soon after dialysis was initiated and that this was associated with a decrease in the expression of cytokeratins and E-cadherin, suggesting that these cells might also contribute to structural changes during PD. Consistent with most previous studies, the results of this study also showed that E-cadherin expression was decreased, while a-SMA expression was increased in HPMCs exposed to HG and in the peritoneum of rats instilled with PD solution, suggesting that PMCs underwent EMT in our in vitro and in vivo experimental models.…”

Endoplasmic reticulum stress as a novel target to ameliorate epithelial-to-mesenchymal transition and apoptosis of human peritoneal mesothelial cells

“…[7][8][9][10][11] Because EMT is known to be a reversible process, it can be a therapeutic target for preserving peritoneal membrane function. 8,9,[11][12][13] In addition to EMT, apoptosis of the peritoneal mesothelial cells is also believed to be one of the early mechanisms of peritoneal damage. The accumulation of misfolded proteins and the induction of endoplasmic reticulum (ER) stress have been implicated in the development of phenotypic transition and apoptosis of epithelial cells.…”