Xiao, J, Gong, Y, Chen, Y, Yu, D, Wang, X, Zhang, X, Dou, Y, Liu, D, Cheng, G, Lu, S, Yuan, W, Li, Y and Zhao, Z (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, 313 (2). F310 - F318. ISSN 1931-857X

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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.

Item Type: Article
Additional Information: The final published version of this article is available online at http://www.physiology.org/doi/10.1152/ajprenal.00428.2016
Uncontrolled Keywords: Peritoneal dialysis, interleukin 6, epithelial-to-mesenchymal 49 transition, human peritoneal mesothelial cells, JAK2/STAT3, WP1066
Subjects: R Medicine > RA Public aspects of medicine
Divisions: Faculty of Medicine and Health Sciences > Primary Care Health Sciences
Related URLs:
Depositing User: Symplectic
Date Deposited: 26 Jan 2018 09:33
Last Modified: 06 Jul 2018 13:25
URI: https://eprints.keele.ac.uk/id/eprint/4406

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