{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T00:14:03Z","timestamp":1792196043933,"version":"4.4.0"},"reference-count":54,"publisher":"Wiley","issue":"21","license":[{"start":{"date-parts":[[2024,7,8]],"date-time":"2024-07-08T00:00:00Z","timestamp":1720396800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82171020"],"award-info":[{"award-number":["82171020"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82201150"],"award-info":[{"award-number":["82201150"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>This study investigated the involvement of discoidin domain receptor (DDR) in dry eye and assessed the potential of specific DDR inhibitors as a therapeutic strategy for dry eye by exploring the underlying mechanism.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Dry eye was induced in Wistar rats by applying 0.2% benzalkonium chloride (BAC), after which rats were treated topically for 7\u2009days with DDR1\u2010IN\u20101, a selective inhibitor of DDR1. Clinical manifestations of dry eye were assessed on Day\u20107 post\u2010treatment. Histological evaluation of corneal damage was performed using haematoxylin and eosin (H&amp;E) staining. In vitro, immortalized human corneal epithelial cells (HCECs) exposed to hyperosmotic stress (HS) were treated with varying doses of DDR1\u2010IN\u20101 for 24\u2009h. The levels of lipid peroxidation in dry eye corneas or HS\u2010stimulated HCECs were assessed. Protein levels of DDR1\/DDR2 and related pathways were detected by western blotting. The cellular distribution of acyl\u2010CoA synthetase long chain family member 4 (ACSL4) and Yes\u2010associated protein (YAP) was evaluated using immunohistochemistry or immunofluorescent staining.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>In dry eye corneas, only DDR1 expression was significantly up\u2010regulated compared with normal controls. DDR1\u2010IN\u20101 treatment significantly alleviated dry eye symptoms in vivo. The treatment remarkably reduced lipid hydroperoxide (LPO) levels and suppressed the expression of ferroptosis markers, particularly ACSL4. Overexpression or reactivation of YAP diminished the protective effects of DDR1\u2010IN\u20101, indicating the involvement of the Hippo\/YAP pathway in DDR1\u2010targeted therapeutic effects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>This study confirms the significance of DDR1 in dry eye and highlights the potential of selective DDR1 inhibitor(s) for dry eye treatment.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.16491","type":"journal-article","created":{"date-parts":[[2024,7,9]],"date-time":"2024-07-09T06:14:04Z","timestamp":1720505644000},"page":"4245-4261","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["A highly selective inhibitor of discoidin domain receptor\u20101 (DDR1\u2010IN\u20101) protects corneal epithelial cells from YAP\/ACSL4\u2010mediated ferroptosis in dry eye"],"prefix":"10.1111","volume":"181","author":[{"given":"Yiqin","family":"Dai","sequence":"first","affiliation":[{"name":"Eye Institute and Department of Ophthalmology Eye &amp; ENT Hospital, Fudan University  Shanghai China"},{"name":"Shanghai Key Laboratory of Visual Impairment and Restoration  Shanghai China"},{"name":"NHC Key Laboratory of Myopia (Fudan University); Key Laboratory of Myopia, Chinese Academy of Medical Sciences  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Li","sequence":"additional","affiliation":[{"name":"Eye Institute and Department of Ophthalmology Eye &amp; ENT Hospital, Fudan University  Shanghai China"},{"name":"Shanghai Key Laboratory of Visual Impairment and Restoration  Shanghai China"},{"name":"NHC Key Laboratory of Myopia (Fudan University); Key Laboratory of Myopia, Chinese Academy of Medical Sciences  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3191-3668","authenticated-orcid":false,"given":"Jianjiang","family":"Xu","sequence":"additional","affiliation":[{"name":"Eye Institute and Department of Ophthalmology Eye &amp; ENT Hospital, Fudan University  Shanghai China"},{"name":"Shanghai Key Laboratory of Visual Impairment and Restoration  Shanghai China"},{"name":"NHC Key Laboratory of Myopia (Fudan University); Key Laboratory of Myopia, Chinese Academy of Medical Sciences  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Eye Institute and Department of Ophthalmology Eye &amp; ENT Hospital, Fudan University  Shanghai China"},{"name":"Shanghai Key Laboratory of Visual Impairment and Restoration  Shanghai China"},{"name":"NHC Key Laboratory of Myopia (Fudan University); Key Laboratory of Myopia, Chinese Academy of Medical Sciences  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,7,8]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.16180"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14112"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.npep.2022.102266"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1167\/tvst.10.11.14"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.survophthal.2021.04.006"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2013.12.002"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2014.04.014"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jproteome.9b00149"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.3109\/02713683.2015.1098707"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14153"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15868"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1188\/16.ONF.235-243"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2008.10.014"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.2013.114"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-022-01191-9"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2021.19963"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells12232755"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-020-00324-8"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtos.2023.04.015"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep35202"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.11-194902"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s12276-020-0446-5"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-800180-6.00002-5"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2022.106368"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm5012319"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15178"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-021-01676-x"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2022.102292"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.122.322113"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11010-022-04644-5"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00417-014-2853-6"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2022.05.005"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.274027.115"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1006\/exer.2000.0932"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.10-7022"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2022.05.004"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3000410"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1080\/09273948.2021.1906908"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24010731"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2024.01.021"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1001\/archophthalmol.2011.364"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/5080843"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.4103\/IJO.IJO_2791_22"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.eye.6700566"},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10555-012-9346-z"},{"key":"e_1_2_12_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2021.02.010"},{"key":"e_1_2_12_48_1","doi-asserted-by":"publisher","DOI":"10.1080\/23723556.2019.1699375"},{"key":"e_1_2_12_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2019.04.003"},{"key":"e_1_2_12_50_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13167-021-00265-y"},{"key":"e_1_2_12_51_1","doi-asserted-by":"publisher","DOI":"10.1080\/09273948.2017.1372486"},{"key":"e_1_2_12_52_1","doi-asserted-by":"publisher","DOI":"10.2147\/JIR.S310116"},{"key":"e_1_2_12_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2024.113926"},{"key":"e_1_2_12_54_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.50663"},{"key":"e_1_2_12_55_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.63.10.3"}],"container-title":["British Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bph.16491","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,2]],"date-time":"2024-10-02T05:48:18Z","timestamp":1727848098000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/bph.16491"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,8]]},"references-count":54,"journal-issue":{"issue":"21","published-print":{"date-parts":[[2024,11]]}},"alternative-id":["10.1111\/bph.16491"],"URL":"https:\/\/doi.org\/10.1111\/bph.16491","archive":["Portico"],"relation":{},"ISSN":["0007-1188","1476-5381"],"issn-type":[{"value":"0007-1188","type":"print"},{"value":"1476-5381","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,8]]},"assertion":[{"value":"2023-12-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-05-26","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-07-08","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}