Active compounds extracted from extra virgin olive oil counteract mesothelial-to-mesenchymal transition of peritoneal mesothelium cells exposed to conventional peritoneal dialysate: in vitro and in vivo evidences

During peritoneal dialysis (PD), peritoneal mesothelial cells undergo a transition from an epithelial phenotype to a mesenchymal phenotype that, together with the inflammatory process, promotes tissue fibrosis and a failure of peritoneal membrane function. To date, there is no definitive treatment for the progressive thickening and angiogenesis of the peritoneal membrane associated with PD. In this study we tested, in vitro and in vivo, the ability of active compounds extracted from extra virgin olive oil (AC-EVOO) to counteract the mesothelial-to-mesenchymal transition process (MMT) observed in mesothelial cells chronically exposed to the conventional peritoneal dialysate (DL). In particular, we used a cultivar from southern Italy known to have a high polyphenol content. Our results showed that, in mesothelial cells exposed to DL, the combined treatment with AC-EVOO prevented the genic and protein upregulation of key mesenchymal and inflammatory markers, as well as the MCs' migratory capacity. Concomitantly, we tested the antifibrotic efficacy of AC-EVOO in mesothelial cells obtained from effluents of patients undergoing PD, whose "fibroblast-like" phenotype was defined by flow-cytometry assay. We observed that in these cells AC-EVOO significantly mitigated, but did not reverse, the MMT process. In conclusion, our preliminary results suggest that AC-EVOO can interfere with critical factors in the process of differentiation, preventing myofibroblast formation, but once fibrosis has already progressed it is unable to promote the redifferentiation to the epithelial phenotype. Further studies are needed to establish whether AC-EVOO could represent a new therapeutic target to prevent peritoneal fibrosis.