IL-6 promotes epithelial-to-mesenchymal transition of human peritoneal mesothelial cells possibly through JAK2/STAT3 signaling pathway.

This study was designed to investigate the role of IL-6 in EMT and peritoneal membrane dysfunction in long-term PD patients by assessing the level of IL-6 in dialysate and exploring the relationship between IL-6, the related signaling pathway JAK2/STAT3, and EMT, using in vitro cellular and molecular techniques. Plasma and dialysate levels of IL-6 were significantly higher in PD ultrafiltration failure patients compared to those in patients without ultrafiltration failure and were negatively correlated with measures of PD adequacy. In vitro, IL-6 treatment changed human peritoneal mesothelial cell phenotype from a typical cobblestone-like to a fibroblast-like appearance and increased cell viability. IL-6 treatment increased α-SMA and VEGF expression but decreased E-cadherin expression. IL-6 treatment activated the JAK/STAT signaling pathway. However, the JAK2/STAT3 inhibitor WP1066 prevented IL-6-induced activation of the JAK2/STAT3 pathway and EMT. We conclude that IL-6 promotes the EMT process, possibly by activating the JAK2/STAT3 signaling pathway. IL-6 may serve as a novel therapeutic target for preventing EMT, and preservation of the peritoneal membrane may arise from these studies. PMID: 28490530 [PubMed - as supplied by publisher]
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research