{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T10:54:30Z","timestamp":1793271270976,"version":"4.5.0"},"reference-count":52,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,1,16]],"date-time":"2024-01-16T00:00:00Z","timestamp":1705363200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81770763"],"award-info":[{"award-number":["81770763"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2024,1,31]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Long\u2010term exposure to non\u2010physiologically compatible dialysate inevitably leads to peritoneal fibrosis (PF) in patients undergoing peritoneal dialysis (PD), and there is no effective prevention or treatment for PF. Sphingosine\u20101\u2010phosphate (S1P) is a bioactive sphingolipid produced after catalysis by sphingosine kinase (SPHK) 1\/2 and activates signals through the S1P receptor (S1PR) via autocrine or paracrine. However, the role of SPHK1\/S1P\/S1PR signaling has never been elucidated in PF. In our research, we investigated S1P levels in peritoneal effluents and demonstrated the role of SPHK1\/S1P\/S1PR pathway in peritoneal fibrosis. It was found that S1P levels in peritoneal effluents were positively correlated with D\/P Cr (\n                    <jats:italic>r<\/jats:italic>\n                    \u2009=\u20090.724,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u2009.001) and negatively correlated with 4 h ultrafiltration volume (\n                    <jats:italic>r<\/jats:italic>\n                    \u2009=\u2009\u22120.457,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u2009.001). S1PR1 and S1PR3 on peritoneal cells were increased after high glucose exposure in\u00a0vivo and in\u00a0vitro. Fingolimod was applied to suppress S1P\/S1PR pathway. Fingolimod restored mouse peritoneal function by reducing interstitial hyperplasia, maintaining ultrafiltration volume, reducing peritoneal transport solute rate, and mitigating the protein expression changes of fibronectin, vimentin, \u03b1\u2010SMA, and E\u2010cadherin induced by PD and S1P. Fingolimod preserved the morphology of the human peritoneal mesothelial cells, MeT\u20105A, and moderated the mesothelial\u2010mesenchymal transition (MMT) process. We further delineated that SPHK1 was elevated in peritoneal cells after high glucose exposure and suppression of SPHK1 in MeT\u20105A cells reduced S1P release. Overexpression of SPHK1 in MeT\u20105A cells increased S1P levels in the supernatant and fostered the MMT process. PF\u2010543 treatment, targeting SPHK1, alleviated deterioration of mouse peritoneal function. In conclusion, S1P levels in peritoneal effluent were correlated with the deterioration of peritoneal function. SPHK1\/S1P\/S1PR pathway played an important role in PF.\n                  <\/jats:p>","DOI":"10.1096\/fj.202301323r","type":"journal-article","created":{"date-parts":[[2024,1,16]],"date-time":"2024-01-16T09:35:16Z","timestamp":1705397716000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["<scp>SPHK1<\/scp>\n                    \/\n                    <scp>S1P<\/scp>\n                    \/\n                    <scp>S1PR<\/scp>\n                    pathway promotes the progression of peritoneal fibrosis by mesothelial\u2010mesenchymal transition"],"prefix":"10.1096","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-1404-879X","authenticated-orcid":false,"given":"Tingting","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Nephrology First Affiliated Hospital of Naval Medical University, Shanghai Changhai Hospital  Shanghai China"},{"name":"Department of Nephrology Shanghai 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