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

Yu

Abstract

Long-term peritoneal dialysis (PD) therapy results in functional and structural alteration of the peritoneal membrane, including epithelial-to-mesenchymal transition (EMT). Interleukin 6 (IL-6) is a local pleiotropic cytokine, hypothesized to play an important role in EMT. 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 with 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 a-smooth muscle actin and vascular endothelial growth factor 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.

Citation

Yu. (2017). IL-6 promotes epithelial-to-mesenchymal transition of human peritoneal mesothelial cells possibly through the JAK2/STAT3 signaling pathway. American journal of physiology. Renal physiology, F310 - F318. https://doi.org/10.1152/ajprenal.00428.2016

• Acceptance Date: Apr 26, 2017
• Publication Date: May 10, 2017
• Journal: American Journal of Physiology - Renal Physiology
• Print ISSN: 1931-857X
• Publisher: American Physiological Society
• Pages: F310 - F318
• DOI: https://doi.org/10.1152/ajprenal.00428.2016
• Keywords: Peritoneal dialysis, interleukin 6, epithelial-to-mesenchymal; 49 transition, human peritoneal mesothelial cells, JAK2/STAT3, WP1066
• Publisher URL: http://www.physiology.org/doi/10.1152/ajprenal.00428.2016