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Increased endothelin\u20101 (ET\u20101) has been observed in aqueous humour (AH) of POAG patients, resulting in an increase in the out\u2010flow resistance of the AH. However, the underlining mechanisms remain elusive. Using established in vivo and in vitro POAG models, we demonstrated that water channel Aquaporin 1 (AQP1) is down\u2010regulated in trabecular meshwork (TM) cells upon ET\u20101 exposure, which causes a series of glaucomatous changes, including actin fibre reorganization, collagen production, extracellular matrix deposition and contractility alteration of TM cells. Ectopic expression of AQP1 can reverse ET\u20101\u2010induced TM tissue remodelling, which requires the presence of \u03b2\u2010catenin. More importantly,\u00a0we found that ET\u20101\u2010induced AQP1 suppression is mediated by ATF4, a transcription factor of the unfolded protein response, which binds to the promoter of <jats:italic>AQP1<\/jats:italic> and negatively regulates <jats:italic>AQP1<\/jats:italic> transcription. Thus, we discovered a novel function of ATF4 in controlling the process of TM remodelling in ET\u20101\u2010induced POAG through transcription suppression of AQP1. Our findings also detail a novel pathological mechanism and a potential therapeutic target for POAG.<\/jats:p>","DOI":"10.1111\/jcmm.15032","type":"journal-article","created":{"date-parts":[[2020,2,13]],"date-time":"2020-02-13T12:41:31Z","timestamp":1581597691000},"page":"3469-3480","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["AQP1 suppression by ATF4 triggers trabecular meshwork tissue remodelling in ET\u20101\u2010induced POAG"],"prefix":"10.1111","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0642-0105","authenticated-orcid":false,"given":"Yingying","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Physiology School of Basic Medical Sciences School of Medicine Shenzhen University Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huazhang","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Physiology School of 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