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

• Published in: American journal of physiology. Renal physiology 2017-08, Vol.313 (2), p.F310-F318
• Main Authors: Xiao, Jing, Gong, Yanan, Chen, Ying, Yu, Dahai, Wang, Xiaoyang, Zhang, Xiaoxue, Dou, Yanna, Liu, Dong, Cheng, Genyang, Lu, Shan, Yuan, Wenming, Li, Yansheng, Zhao, Zhanzheng
• Format: Article
• Language: English
• Subjects: Actin; Actins - metabolism; Adult; Cadherins - metabolism; Cell Shape; Cell Survival; Cells; Cells, Cultured; Dialysis Solutions - metabolism; Dose-Response Relationship, Drug; E-cadherin; Epithelial-Mesenchymal Transition - drug effects; Female; Genotype & phenotype; Hemodialysis; Humans; Interleukin 6; Interleukin-6 - blood; Interleukin-6 - toxicity; Janus kinase 2; Janus Kinase 2 - metabolism; Kidney Failure, Chronic - blood; Kidney Failure, Chronic - diagnosis; Kidney Failure, Chronic - therapy; Male; Membranes; Mesenchyme; Middle Aged; Peritoneal dialysis; Peritoneal Dialysis - adverse effects; Peritoneum; Peritoneum - drug effects; Peritoneum - enzymology; Peritoneum - pathology; Phenotype; Preservation; Signal transduction; Signal Transduction - drug effects; Smooth muscle; Stat3 protein; STAT3 Transcription Factor - metabolism; Structure-function relationships; Time Factors; Ultrafiltration; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - metabolism
• ISSN: 1931-857X; 1522-1466
• DOI: 10.1152/ajprenal.00428.2016

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 α-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.