{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T04:58:01Z","timestamp":1793509081793,"version":"4.5.0"},"reference-count":84,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,4,11]],"date-time":"2017-04-11T00:00:00Z","timestamp":1491868800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,4,11]],"date-time":"2017-04-11T00:00:00Z","timestamp":1491868800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Fundamental cell signaling mechanisms that regulate dynamic remodeling of the extracellular matrix (ECM) in mechanically loaded tissues are not yet clearly understood. Trabecular meshwork (TM) tissue in the eye is under constant mechanical stress and continuous remodeling of ECM is crucial to maintain normal aqueous humor drainage and intraocular pressure (IOP). However, excessive ECM remodeling can cause fibrosis of the TM as in primary open-angle glaucoma (POAG) patients, and is characterized by increased resistance to aqueous humor drainage, elevated IOP, optic nerve degeneration and blindness. Increased levels of active transforming growth factor-\u03b22 (TGF-\u03b22) in the aqueous humor is the main cause of fibrosis of TM in POAG patients. Herein, we report a novel finding that, in TM cells, TGF-\u03b2-induced increase in collagen expression is associated with phosphorylation of phosphatase and tensin homolog (PTEN) at residues Ser380\/Thr382\/383. Exogenous overexpression of a mutated form of PTEN with enhanced phosphatase activity prevented the TGF-\u03b2-induced collagen expression by TM cells. We propose that rapid alteration of PTEN activity through changes in its phosphorylation status could uniquely regulate the continuous remodeling of ECM in the normal TM. Modulating PTEN activity may have high therapeutic potential to alleviating the fibrosis of TM in POAG patients.<\/jats:p>","DOI":"10.1038\/s41598-017-00845-x","type":"journal-article","created":{"date-parts":[[2017,4,5]],"date-time":"2017-04-05T14:29:41Z","timestamp":1491402581000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["TGF-\u03b2 induces phosphorylation of phosphatase and tensin homolog: implications for fibrosis of the trabecular meshwork tissue in glaucoma"],"prefix":"10.1038","volume":"7","author":[{"given":"Nikoleta","family":"Tellios","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jillian C.","family":"Belrose","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander C.","family":"Tokarewicz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cindy","family":"Hutnik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Leask","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Motolko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miho","family":"Iijima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunil K.","family":"Parapuram","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,4,11]]},"reference":[{"key":"845_CR1","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1242\/dmm.004077","volume":"4","author":"TR Cox","year":"2011","unstructured":"Cox, T. 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Differential regulation of membrane type 1-matrix metalloproteinase activity by ERK 1\/2- and p38 MAPK-modulated tissue inhibitor of metalloproteinases 2 expression controls transforming growth factor-beta1-induced pericellular collagenolysis. J Biol Chem \n                           279, 39042\u201339050, doi:10.1074\/jbc.M404958200 (2004).","journal-title":"J Biol Chem"},{"key":"845_CR8","doi-asserted-by":"publisher","first-page":"e70595","DOI":"10.1371\/journal.pone.0070595","volume":"8","author":"H Han","year":"2013","unstructured":"Han, H., Kampik, D., Grehn, F. & Schlunck, G. TGF-beta2-induced invadosomes in human trabecular meshwork cells. PLoS One \n                           8, e70595, doi:10.1371\/journal.pone.0070595 (2013).","journal-title":"PLoS One"},{"key":"845_CR9","first-page":"1375","volume":"25","author":"ES Kim","year":"2004","unstructured":"Kim, E. S., Kim, M. S. & Moon, A. 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