{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T18:14:24Z","timestamp":1790792064505,"version":"4.1.0"},"reference-count":68,"publisher":"American Society for Clinical Investigation","issue":"22","license":[{"start":{"date-parts":[[2024,11,22]],"date-time":"2024-11-22T00:00:00Z","timestamp":1732233600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Shanghai Industrial Collaborative Technology Innovation Project","award":["XTCX-KJ-2022-35"],"award-info":[{"award-number":["XTCX-KJ-2022-35"]}]},{"name":"the Science and Technology Commission of Shanghai","award":["19411961500"],"award-info":[{"award-number":["19411961500"]}]},{"name":"the Clinical Research Program of 9th People\u2019s Hospital affiliated to Shanghai Jiao Tong University School of Medicine","award":["JYLJ201804"],"award-info":[{"award-number":["JYLJ201804"]}]},{"name":"the Natural Science Research Project of Anhui Educational 500 Committee","award":["KJ2021A0766"],"award-info":[{"award-number":["KJ2021A0766"]}]},{"DOI":"10.13039\/501100001809","name":"the National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82371054"],"award-info":[{"award-number":["82371054"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,11,22]]},"abstract":"<jats:p>Accumulation of extracellular matrix (ECM) proteins in trabecular meshwork (TM), which leads to increased outflow resistance of aqueous humor and consequently high intraocular pressure, is a major cause of primary open-angle glaucoma (POAG). According to our preliminary research, the RapGAP protein superfamily member, signal-induced proliferation-associated 1-like 1 protein (SIPA1L1), which is involved in tissue fibrosis, may have an impact on POAG by influencing ECM metabolism of TM. This study aims to confirm these findings and identify effects and cellular mechanisms of SIPA1L1 on ECM changes and phagocytosis in human TM (HTM) cells. Our results showed that the expression of SIPA1L1 in HTM cells was significantly increased by TGF-\u03b22 treatment in label-free quantitative proteomics. The aqueous humor and TM cell concentration of SIPA1L1 in POAG patients was higher than that of control. In HTM cells, TGF-\u03b22 increased expression of SIPA1L1 along with accumulation of ECM, RhoA, and p-cofilin 1. The effects of TGF-\u03b22 were reduced by si-SIPA1L1. TGF-\u03b22 decreased HTM cell phagocytosis by polymerizing cytoskeletal actin filaments, while si-SIPA1L1 increased phagocytosis by disassembling actin filaments. Simultaneously, overexpressing SIPA1L1 alone exhibited comparable effects to that of TGF-\u03b22. Our studies demonstrate that SIPA1L1 not only promotes the production of ECM, but also inhibits its removal by reducing phagocytosis. Targeting SIPA1L1 degradation may become a significant therapy for POAG.<\/jats:p>","DOI":"10.1172\/jci.insight.174836","type":"journal-article","created":{"date-parts":[[2024,10,3]],"date-time":"2024-10-03T12:00:11Z","timestamp":1727956811000},"source":"Crossref","is-referenced-by-count":10,"title":["Effects of SIPA1L1 on trabecular meshwork extracellular matrix protein accumulation and cellular phagocytosis in POAG"],"prefix":"10.1172","volume":"9","author":[{"given":"Chenyu","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Ninth People\u2019s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China."},{"name":"Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China."},{"name":"Bengbu Medical University, Bengbu, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiahong","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Songjiang Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Ninth People\u2019s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China."},{"name":"Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China."},{"name":"Bengbu Medical University, Bengbu, China."},{"name":"Department of Ophthalmology, Tongji Hospital, Tongji University School of Medicine, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyu","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Tongji Hospital, Tongji University School of Medicine, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingmin","family":"Hou","sequence":"additional","affiliation":[{"name":"Bengbu Medical University, Bengbu, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuchen","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, First Affiliated Hospital of Bengbu Medical College, Bengbu, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Guo","sequence":"additional","affiliation":[{"name":"Lu\u2019an Hospital Affiliated to Anhui Medical University, Lu\u2019an, China."},{"name":"Lu\u2019an People\u2019s Hospital, Lu\u2019an, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Ninth People\u2019s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China."},{"name":"Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6808-064X","authenticated-orcid":true,"given":"Tao","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Ninth People\u2019s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China."},{"name":"Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2024,11,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2014.3192"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2014.05.013"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1136\/bjo.2005.081224"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1136\/bjophthalmol-2014-306102"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2012.09.014"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2020.21899"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)31469-1"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2016.08.001"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1604153113"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1136\/bjophthalmol-2016-309883"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2020.107920"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1007\/s00417-019-04300-7"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2015.09.005"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2014.07.014"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1007\/s00427-016-0556-1"},{"issue":"2","key":"B16","first-page":"321","article-title":"An Epha4\/Sipa1l3\/Wnt pathway regulates eye development and lens maturation","volume":"144","author":"Rothe","year":"2017","journal-title":"Development"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.13353"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddv298"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1002\/ana.25426"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2015.46"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2007.02.009"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M117.779611"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2746-07.2007"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.4161\/cam.27352"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.15-17438"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines9010035"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.17-22807"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1080\/02713683.2020.1815791"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2020.00302"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1818808116"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.61.6.45"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1242\/bio.018887"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.30953"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2022.886754"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1186\/s12886-019-1183-1"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.19-27091"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-81048-3"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1186\/s12929-021-00745-3"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1007\/s004170000252"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1002\/term.2488"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.19-26585"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.61.10.38"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2022.109350"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2020.588347"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2018.06.038"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-13573-8"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.13-12084"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-019-0414-2"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1080\/21505594.2018.1528841"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-019-03096-6"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2016.08.009"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.01066"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-022-03295-y"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2018.03.001"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-23861-x"},{"key":"B56"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1906643116"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.14348\/molcells.2016.0112"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.18632\/aging.202677"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2022.886702"},{"key":"B61","first-page":"237","article-title":"Genomic\/proteomic analyses of dexamethasone-treated human trabecular meshwork cells reveal a role for GULP1 and ABR in phagocytosis","volume":"25","author":"Faralli","year":"2019","journal-title":"Mol Vis"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2016.08.023"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1201330"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M116.736140"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.3858\/emm.2010.42.5.035"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.1322"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.M113.031591"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1002\/imt2.85"}],"container-title":["JCI Insight"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/insight.jci.org\/articles\/view\/174836\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T20:37:09Z","timestamp":1779136629000},"score":1,"resource":{"primary":{"URL":"https:\/\/insight.jci.org\/articles\/view\/174836"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,22]]},"references-count":68,"journal-issue":{"issue":"22","published-online":{"date-parts":[[2024,11,22]]},"published-print":{"date-parts":[[2024,11,22]]}},"alternative-id":["10.1172\/jci.insight.174836"],"URL":"https:\/\/doi.org\/10.1172\/jci.insight.174836","relation":{},"ISSN":["2379-3708"],"issn-type":[{"value":"2379-3708","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,22]]},"article-number":"e174836"}}