{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T12:14:48Z","timestamp":1789906488708,"version":"4.0.1"},"reference-count":51,"publisher":"American Physiological Society","issue":"2","funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81370864"],"award-info":[{"award-number":["81370864"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81670691"],"award-info":[{"award-number":["81670691"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004894","name":"Shanghai Municipal Education Commission | E-Institutes of Shanghai Municipal Education Commission","doi-asserted-by":"publisher","award":["20152211"],"award-info":[{"award-number":["20152211"]}],"id":[{"id":"10.13039\/501100004894","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Renal Physiology"],"published-print":{"date-parts":[[2020,2,1]]},"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.1152\/ajprenal.00319.2019","type":"journal-article","created":{"date-parts":[[2019,12,16]],"date-time":"2019-12-16T18:00:26Z","timestamp":1576519226000},"page":"F338-F353","source":"Crossref","is-referenced-by-count":46,"title":["IL-6<i>trans-<\/i>signaling drives a STAT3-dependent pathway that leads to structural alterations of the peritoneal membrane"],"prefix":"10.1152","volume":"318","author":[{"given":"Xiaoxiao","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Nephrology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Center for Peritoneal Dialysis Research, Shanghai, 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