{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T17:15:00Z","timestamp":1786986900560,"version":"build-2736575974"},"reference-count":177,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2020,6,10]],"date-time":"2020-06-10T00:00:00Z","timestamp":1591747200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>In chronic peritoneal diseases, mesothelial-mesenchymal transition is determined by cues from the extracellular environment rather than just the cellular genome. The transformation of peritoneal mesothelial cells and other host cells into myofibroblasts is mediated by cell membrane receptors, Transforming Growth Factor \u03b21 (TGF-\u03b21), Src and Hypoxia-inducible factor (HIF). This article provides a narrative review of the reprogramming of mesothelial mesenchymal transition in chronic peritoneal diseases, drawing on the similarities in pathophysiology between encapsulating peritoneal sclerosis and peritoneal metastasis, with a particular focus on TGF-\u03b21 signaling and estrogen receptor modulators. Estrogen receptors act at the cell membrane\/cytosol as tyrosine kinases that can phosphorylate Src, in a similar way to other receptor tyrosine kinases; or can activate the estrogen response element via nuclear translocation. Tamoxifen can modulate estrogen membrane receptors, and has been shown to be a potent inhibitor of mesothelial-mesenchymal transition (MMT), peritoneal mesothelial cell migration, stromal fibrosis, and neoangiogenesis in the treatment of encapsulating peritoneal sclerosis, with a known side effect and safety profile. The ability of tamoxifen to inhibit the transduction pathways of TGF-\u03b21 and HIF and achieve a quiescent peritoneal stroma makes it a potential candidate for use in cancer treatments. This is relevant to tumors that spread to the peritoneum, particularly those with mesenchymal phenotypes, such as colorectal CMS4 and MSS\/EMT gastric cancers, and pancreatic cancer with its desmoplastic stroma. Morphological changes observed during mesothelial mesenchymal transition can be treated with estrogen receptor modulation and TGF-\u03b21 inhibition, which may enable the regression of encapsulating peritoneal sclerosis and peritoneal metastasis.<\/jats:p>","DOI":"10.3390\/ijms21114158","type":"journal-article","created":{"date-parts":[[2020,6,15]],"date-time":"2020-06-15T03:17:32Z","timestamp":1592191052000},"page":"4158","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Reprogramming of Mesothelial-Mesenchymal Transition in Chronic Peritoneal Diseases by Estrogen Receptor Modulation and TGF-\u03b21 Inhibition"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7408-4695","authenticated-orcid":false,"given":"Robert B.","family":"Wilson","sequence":"first","affiliation":[{"name":"Department of Upper Gastrointestinal Surgery, UNSW, Liverpool Hospital, Liverpool NSW 2170, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0814-7723","authenticated-orcid":false,"given":"Rami","family":"Archid","sequence":"additional","affiliation":[{"name":"Department of General and Transplant Surgery, National Center for Pleura and Peritoneum, University Hospital T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc A.","family":"Reymond","sequence":"additional","affiliation":[{"name":"Department of General and Transplant Surgery, National Center for Pleura and Peritoneum, University Hospital T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,6,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"20180103","DOI":"10.1515\/pp-2018-0103","article-title":"Hypoxia, cytokines and stromal recruitment: Parallels between pathophysiology of encapsulating peritoneal sclerosis, endometriosis and peritoneal metastasis","volume":"3","author":"Wilson","year":"2018","journal-title":"Pleura Peritoneum"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/s12986-017-0178-2","article-title":"Press-pulse: A novel therapeutic strategy for the metabolic management of cancer","volume":"14","author":"Seyfried","year":"2017","journal-title":"Nutr. 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