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Recent evidence indicates that signal transducer and activator of transcription 3 (STAT3) might mediate the process of renal fibrosis, which could induce the expression of hypoxia-inducible factor-1\u03b1 (HIF-1\u03b1). Here, we investigated the effect of STAT3 activation on HIF-1\u03b1 expression and the EMT of mesothelial cells, furthermore the role of pharmacological blockade of STAT3 in the process of PF during peritoneal dialysis (PD) treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Firstly, we investigated the STAT3 signaling in human peritoneal\u00a0mesothelial cells (HPMCs)\u00a0from drained PD effluent. Secondly, we explored the effect of STAT3 signaling activation on the EMT and the expression of HIF-1\u03b1 in human mesothelial cells (Met-5A) induced by high glucose. Finally, peritoneal fibrosis was induced by daily intraperitoneal injection with peritoneal dialysis\u00a0fluid (PDF) so as to explore the role of pharmacological blockade of STAT3 in this process.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Compared with the new PD patient, the level of phosphorylated STAT3 was up-regulated in peritoneal mesothelial cells from long-term PD patients. High glucose (60\u00a0mmol\/L) induced over-expression of Collagen I, Fibronectin, \u03b1-SMA and reduced the\u00a0expression of E-cadherin in Met-5A cells, which could be abrogated by STAT3 inhibitor S3I-201 pretreatment as well as by siRNA for STAT3. Furthermore, high glucose-mediated STAT3 activation in mesothelial cells induced the expression of HIF-1\u03b1 and the profibrotic effect of STAT3 signaling was alleviated by siRNA for HIF-1\u03b1. Daily intraperitoneal injection of high-glucose based dialysis fluid (HG-PDF) induced peritoneal fibrosis in the mice, accompanied by the phosphorylation of STAT3. Immunostaining showed that phosphorylated STAT3 was expressed mostly in \u03b1-SMA positive cells in the peritoneal membrane induced by HG-PDF. Administration of S3I-201 prevented the progression of peritoneal fibrosis, angiogenesis, macrophage infiltration as well as the expression of HIF-1\u03b1 in the peritoneal membrane induced by high glucose.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Taken together, these findings identified a novel mechanism linking STAT3\/HIF-1\u03b1 signaling to peritoneal fibrosis during long-term PD treatment. It provided the first evidence that pharmacological inhibition of STAT3 signaling attenuated high glucose-mediated mesothelial cells EMT as well as peritoneal fibrosis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12967-021-02946-8","type":"journal-article","created":{"date-parts":[[2021,6,30]],"date-time":"2021-06-30T08:03:23Z","timestamp":1625040203000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["STAT3\/HIF-1\u03b1 signaling activation mediates peritoneal fibrosis induced by high glucose"],"prefix":"10.1186","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5828-7970","authenticated-orcid":false,"given":"Xiaoxiao","family":"Yang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manchen","family":"Bao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Fang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofang","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Ji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqiang","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,6,30]]},"reference":[{"issue":"3","key":"2946_CR1","doi-asserted-by":"publisher","first-page":"498","DOI":"10.1093\/oxfordjournals.ndt.a027318","volume":"11","author":"SJ Davies","year":"1996","unstructured":"Davies SJ, Bryan J, Phillips L, Russell GI. 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