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Tamoxifen (TAM), an inhibitor of estrogen receptor 1 (ESR1), has been reported to treat fibrosis, but the underlying mechanism remains unknown. In this study, we sought to explore whether tamoxifen played an anti-fibrotic role by affecting transcription factor ESR1.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>ESR1 expression was detected in the human peritoneum. Mice were daily intraperitoneally injected with 4.25% glucose PD dialysate containing 40\u00a0mM methylglyoxal for 2\u00a0weeks to establish PD-induced peritoneal fibrosis. Tamoxifen was administrated by daily gavage, at the dose of 10\u00a0mg\/kg. Chromatin immunoprecipitation (ChIP) and dual\u2010luciferase reporter assay were performed to validate ESR1 bound <jats:italic>H19<\/jats:italic> promoter. Gain-of-function and loss-of-function experiments were performed to investigate the biological roles of H19 on the mesothelial-mesenchymal transition (MMT) of human peritoneal mesothelial cells (HPMCs). Intraperitoneal injection of nanomaterial-wrapped 2\u2032-<jats:italic>O<\/jats:italic>-Me-modified small interfering RNA was applied to suppress H19 in the mouse peritoneum. RNA immunoprecipitation and RNA pull-down assays demonstrated binding between H19 and p300. Exfoliated peritoneal cells were obtained from peritoneal dialysis effluent to analyze the correlations between ESR1 (or H19) and peritoneal solute transfer rate (PSTR).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>ESR1 was increased significantly in the peritoneum after long-term exposure to PD dialysate. Tamoxifen treatment ameliorated high glucose-induced MMT of HPMCs, improved ultrafiltration rate, and decreased PSTR of mouse peritoneum. Tamoxifen reduced the H19 level by decreasing the ESR1 transcription of <jats:italic>H19<\/jats:italic>. Depletion of H19 reversed the pro-fibrotic effect of high glucose while ectopic expression of H19 exacerbated fibrotic pathological changes. Intraperitoneal injection of nanomaterial-wrapped 2\u2032-<jats:italic>O<\/jats:italic>-Me-modified siRNAs targeting H19 mitigated PD-related fibrosis in mice. RNA immunoprecipitation (RIP) and RNA pull-down results delineated that H19 activated VEGFA expression by binding p300 to the <jats:italic>VEGFA<\/jats:italic> promoter and inducing histone acetylation of the <jats:italic>VEGFA<\/jats:italic> promoter. ESR1 and H19 were promising targets to predict peritoneal function.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>High glucose-induced MMT of peritoneal mesothelial cells in peritoneal dialysis via activating ESR1. In peritoneal mesothelial cells, ESR1 transcribed the <jats:italic>H19<\/jats:italic> and H19 binds to transcription cofactor p300 to activate the <jats:italic>VEGFA<\/jats:italic>. Targeting ESR1\/H19\/VEGFA pathway provided new hope for patients undergoing peritoneal dialysis.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Graphic Abstract<\/jats:title>\n                \n              <\/jats:sec>","DOI":"10.1186\/s12967-023-04470-3","type":"journal-article","created":{"date-parts":[[2023,9,11]],"date-time":"2023-09-11T10:02:16Z","timestamp":1694426536000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Tamoxifen exerts anti-peritoneal fibrosis effects by inhibiting H19-activated VEGFA transcription"],"prefix":"10.1186","volume":"21","author":[{"given":"Tingting","family":"Zhao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengyu","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueli","family":"Lai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongtao","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lulu","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuangxi","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji-hang","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7816-3270","authenticated-orcid":false,"given":"Zhiyong","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,9,11]]},"reference":[{"issue":"19","key":"4470_CR1","doi-asserted-by":"publisher","first-page":"1786","DOI":"10.1056\/NEJMra2100152","volume":"385","author":"I Teitelbaum","year":"2021","unstructured":"Teitelbaum I. 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Mol Cancer. 2014;13:91. https:\/\/doi.org\/10.1186\/1476-4598-13-91.","journal-title":"Mol Cancer"}],"container-title":["Journal of Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12967-023-04470-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12967-023-04470-3\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12967-023-04470-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,18]],"date-time":"2023-11-18T16:32:53Z","timestamp":1700325173000},"score":1,"resource":{"primary":{"URL":"https:\/\/translational-medicine.biomedcentral.com\/articles\/10.1186\/s12967-023-04470-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,11]]},"references-count":40,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["4470"],"URL":"https:\/\/doi.org\/10.1186\/s12967-023-04470-3","relation":{"references":[{"id-type":"uri","id":"","asserted-by":"subject"}]},"ISSN":["1479-5876"],"issn-type":[{"value":"1479-5876","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,11]]},"assertion":[{"value":"16 May 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 August 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 September 2023","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All patients were informed and consented to the procedure. The Shanghai Changhai Hospital Ethics Committee approved our study in accordance with the protocol, and the principles of research ethics as the Declaration of Helsinki (NO.CHBC2020-096, Date: 8th November 2021)<b>.<\/b>All experimental procedures involving animals were conducted in accordance with the Basel Declaration and were approved by the ethics committee of Naval Medical University (NO.NMUMREC-2021-006, Date: 10th March 2021).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"All presentations of case reports have consent for publication.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"All the authors declared no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"614"}}