{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T04:48:46Z","timestamp":1781585326668,"version":"3.54.5"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2021,5,13]],"date-time":"2021-05-13T00:00:00Z","timestamp":1620864000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100001691","name":"KAKENHI","doi-asserted-by":"publisher","award":["Grant-in-Aid for Scientific Research: 15K10694 to K.T. and 20H03133 to K.K"],"award-info":[{"award-number":["Grant-in-Aid for Scientific Research: 15K10694 to K.T. and 20H03133 to K.K"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,5,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Endometriosis is characterised by inflammation and fibrotic changes. Our previous study using a mouse model showed that proinflammatory factors present in peritoneal haemorrhage exacerbated inflammation in endometriosis-like grafts, at least in part through the activation of prostaglandin (PG) E2 receptor and protease-activated receptor (PAR). In addition, hypoxia is a well-known inducer of fibrosis that may be associated with epithelial\u2013mesenchymal transition (EMT). However, the complex molecular interactions between hypoxia and proinflammatory menstruation-related factors, PGE2 and thrombin, a PAR1 agonist, on EMT in endometriosis have not been fully characterised. To explore the effects of hypoxia and proinflammatory factors on EMT-like changes in endometrial cells, we determined the effects of PGE2 and thrombin (P\/T) on EMT marker expression and cell migration in three dimensional cultured human endometrial epithelial cells (EECs) and endometrial stromal cells (ESCs). Treatment of EECs with P\/T under hypoxia stimulated cell migration, increased the expression of mesenchymal N-cadherin, vimentin and C-X-C chemokine receptor type 4 (CXCR4), and reduced the expression of epithelial E-cadherin. Furthermore, treatment with C-X-C motif chemokine ligand 12 (CXCL12), a ligand for CXCR4, increased EMT marker expression and cell migration. In ESCs, P\/T or oestrogen treatment under hypoxic conditions increased the expression and secretion of CXCL12. Taken together, our data show that hypoxic and proinflammatory stimuli induce EMT, cell migration and inflammation in EECs, which was increased by CXCL12 derived from ESCs. These data imply that inflammatory mediators in retrograde menstrual fluid contribute to ectopic endometrial EMT and migration in the presence of peritoneal hypoxia.<\/jats:p>","DOI":"10.1093\/molehr\/gaab036","type":"journal-article","created":{"date-parts":[[2021,5,12]],"date-time":"2021-05-12T11:26:47Z","timestamp":1620818807000},"source":"Crossref","is-referenced-by-count":29,"title":["Endometrial epithelial\u2013mesenchymal transition (EMT) by menstruation-related inflammatory factors during hypoxia"],"prefix":"10.1093","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9120-0475","authenticated-orcid":false,"given":"K","family":"Kusama","sequence":"first","affiliation":[{"name":"Department of Endocrine Pharmacology, Tokyo University of Pharmacy and Life Sciences, Tokyo 192-0392, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y","family":"Fukushima","sequence":"additional","affiliation":[{"name":"Department of Endocrine Pharmacology, Tokyo 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