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Because autotaxin (ATX) is upregulated in SOAG, we investigated the relationships and trans-signaling interactions of these mediators.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>The level of ATX in AH was determined using a two-site immunoenzymetric assay, and TGF-\u03b2 levels were measured using the Bio-Plex Pro TGF-\u03b2 Assay. RNA scope was used to assess the expression of ATX and TGF-\u03b22 in human\u2019s eye specimen. And in vitro studies were performed using hTM cells to explore if trans-signaling of TGF-\u03b22 regulates ATX expressions.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>TGF-\u03b22\/ATX ratio was significantly high in AH of control or POAG compared with SOAG, and negatively correlated with IOP. RNA scope revelated positive expressions of both TGF-\u03b22 and ATX in ciliary body (CB) and TM in control, but ATX expressions was significantly enhanced in SOAG. In hTM cells, ATX expressions were regulated by TGF-\u03b22 with concentration-dependent manner. In counter, ATX also induced TGF-\u03b21, TGF-\u03b22 and TGFBI upregulations and activation of the Smad-sensitive promoter, as well as upregulation of fibrotic markers, and these upregulation was significantly suppressed by both TGF-\u03b2 and ATX inhibition.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Trans-signaling of TGF-\u03b22 regulates ATX expressions and thereby induced upregulations of TGF-\u03b2s or fibrosis of hTM. TGF-\u03b22 trans-signaling potently regulate ATX transcription and signaling in hTM cells, which may reflect different profile of these mediators in glaucoma subtypes.<\/jats:p>\n                <jats:p><jats:italic>Trial Registration<\/jats:italic> This prospective observational study was approved by the Institutional Review Board of the University of Tokyo and was registered with the University Hospital Medical Information Network Clinical Trials Registry of Japan (ID: UMIN000027137). All study procedures conformed to the Declaration of Helsinki. Written informed consent was obtained from each patient.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12929-021-00745-3","type":"journal-article","created":{"date-parts":[[2021,6,17]],"date-time":"2021-06-17T16:06:47Z","timestamp":1623946007000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Crosstalk between transforming growth factor \u03b2-2 and Autotaxin in trabecular meshwork and different subtypes of glaucoma"],"prefix":"10.1186","volume":"28","author":[{"given":"Nozomi","family":"Igarashi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2383-8255","authenticated-orcid":false,"given":"Megumi","family":"Honjo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reiko","family":"Yamagishi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Kurano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutaka","family":"Yatomi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koji","family":"Igarashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshikatsu","family":"Kaburaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Aihara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,6,17]]},"reference":[{"issue":"3","key":"745_CR1","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1136\/bjo.2005.081224","volume":"90","author":"HA Quigley","year":"2006","unstructured":"Quigley HA, Broman AT. 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