IL-6 trans-signaling drives a STAT3-dependent pathway that leads to structural alterations of the peritoneal membrane
IL-6 trans-signaling drives a STAT3-dependent pathway that leads to structural alterations of the peritoneal membrane
复制标题
IL-6 反式信号传导驱动 STAT3 依赖性途径，导致腹膜结构改变
DOI：
10.1152/ajprenal.00319.2019
复制
发表时间：
2020-02-01
影响因子：
4.2
通讯作者：
Fang, Wei
中科院分区：
文献类型：
--
作者：
Yang, Xiaoxiao;Yan, Hao;Fang, Wei
IL-6 is a vital inflammatory factor in the peritoneal cavity of patients undergoing peritoneal dialysis (PD). The present study examined the effect of IL-6 trans-signaling on structural alterations of the peritoneal membrane. We investigated whether the epithelial-to-mesenchymal transition (EMT) process of human peritoneal mesothelial cells (HPMCs) and the production of proangiogenic factors were controlled by IL-6 trans-signaling. Its role in the peritoneal alterations was detected in a mouse model. The morphology of HPMCs and levels of cytokines in PD effluent were also explored. Stimulation of HPMCs with the IL-6 and soluble IL-6 receptor complex (IL-6/S) promoted the EMT process of HPMCs depending on the STAT3 pathway. In a coculture system of HPMCs and human umbilical vein endothelial cells, IL-6/S mediated the production of VEGF and angiopoietins so as to downregulate the expression of endothelial junction molecules and finally affect vascular permeability. Daily intraperitoneal injection of high glucose-based dialysis fluid induced peritoneal fibrosis. angiogenesis, and macrophage infiltration in a mouse model, accompanied by phosphorylation of STAT3. Blockade of IL-6 trans-signaling prevented these peritoneum alterations. The fibroblast-like appearance of HPMCs ex vivo was upregulated in patients undergoing prevalent PD accompanied by increasing levels of IL-6, VEGF, and angiopoietin-2 in the PD effluent. Taken together, these findings identified a critical link between IL-6 trans-signaling and structural alterations of the peritoneal membrane, and it might be a potential target for the treatment of patients undergoing PD who have developed peritoneal alterations.
