Nestin+ Cells Isolated From the Peritoneum Ameliorate Peritoneal Fibrosis Development

Abstract The intermediate filament protein Nestin, a specific marker for multifunctional, multilineage progenitor cells, is regulated during the progression of reparative and reactive fibrosis in the liver, heart and kidney. In this study, Nestin was found in both the mouse peritoneum and HPMCs derived from PD effluent (PDE) and HMrSV5. Moreover, these Nestin+ PMCs showed extensive proliferation for more than 20 passages. The mice that received chronic peritoneal dialysis solution (PDS) infusions showed typical features of peritoneal fibrosis (PF), including substantially increased perito­neal thickness, excessive matrix deposition, increased peritoneal permeability, and increased expression levels of α-smooth muscle actin (α-SMA) and collagen I (Col I). Nestin+ cells isolated from the peritoneum could significantly ameliorate these pathological changes. A parallel decrease in interleukin-33 (IL-33) and ST-2 accumulation in the peritoneum of Nestin+ cell-transplanted mice was observed. In addition, downregulation of IL-33 expression decreasedTGF-β1-induced accumulation of extracellular matrix (ECM) in the HPMCs. In conclusion, our findings discover a novel mechanism of Nestin+ cells in PF, that is, Nestin+ cells isolated from the peritoneum probably had a protective effect on high-glucose PDS-induced PF by suppressing IL-33/ST-2 signaling.