Details

Autor(en) / Beteiligte

• Wu, Jun
• Zhang, Yun-Fang
• Li, Ju-Shuang
• Zhu, Ge-Li
• Bi, Zhi-Min
• Li, Xiang-You

Titel

The effect of high glucose-based peritoneal dialysis fluids on thioredoxin-interacting protein expression in human peritoneal mesothelial cells

Ist Teil von

• International immunopharmacology, 2019-01, Vol.66, p.198-204

Ort / Verlag

Netherlands: Elsevier B.V

Erscheinungsjahr

2019

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• It has been demonstrated that thioredoxin-interacting protein (TXNIP) interacted with NACHT, LRR and PYD domains-containing protein 3 (NLRP3) and participated in the NLRP3 inflammasome activation. Our previous study has demonstrated that in human peritoneal mesothelial cells (HPMCs), exposure to high glucose-based peritoneal dialysis (PD) solutions induced mitochondrial reactive oxygen species (ROS) production, activation of NLRP3 inflammasome and IL-1β expression. This study aimed to investigate the effect of high glucose-based PD fluids on the TXNIP expression and the underlying mechanisms by which TXNIP-NLRP3 interaction mediates the inflammatory injury to HPMCs in high glucose-based PD fluids conditions. TXNIP gene and protein expression was detected by real-time polymerase chain reaction (RT-PCR) and immunoblot. Immunoprecipitation was used to evaluate the interaction between TRX1 and TXNIP, TXNIP and NLRP3. ROS production and IL-1β expression was examined by flow cytometry and immunoblot and enzyme-linked immunosorbent assay (ELISA) respectively. It was identified that high glucose-based PD solutions enhance the level of TXNIP gene and protein in cultured HPMCs and a rat-based PD model. We also found that ROS generation induced by high glucose-based PD solutions disrupts the TRX1-TXNIP association, while promoting the binding of TXNIP to NLRP3 in HPMCs. Furthermore, the application of a ROS inhibitor (APDC) to HPMCs blocked the high glucose-based PD solution-induced TXNIP-NLRP3 binding, in addition to ROS production and IL-1β expression. The results of the present study revealed a novel mechanism underlying high glucose-containing PD-mediated peritoneal inflammatory injury, supporting the attenuation of ROS generation as a potential therapeutic strategy to alleviate such pathology. •High glucose-based peritoneal dialysis (PD) fluids upregulate TXNIP expression in vitro and in vivo.•High glucose-based PD fluids disrupt TRX1-TXNIP association and enhance TXNIP-NLRP3 interaction.•Inhibition of ROS blocks TXNIP-NLRP3 binding and decreases IL-1β expression induced by high glucose-based PD fluids.