{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T22:01:42Z","timestamp":1791928902032,"version":"4.3.4"},"reference-count":63,"publisher":"Association for Research in Vision and Ophthalmology (ARVO)","issue":"6","license":[{"start":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T00:00:00Z","timestamp":1780963200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Invest. Ophthalmol. Vis. Sci."],"published-print":{"date-parts":[[2026,6,9]]},"DOI":"10.1167\/iovs.67.6.14","type":"journal-article","created":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T12:30:43Z","timestamp":1781008243000},"page":"14","source":"Crossref","is-referenced-by-count":1,"title":["NEDD8 Promotes the Progression and Inflammation of Keratoconus by Increasing the Expression of YAP1"],"prefix":"10.1167","volume":"67","author":[{"given":"Junpeng","family":"Qu","sequence":"first","affiliation":[{"name":"Medical College, Qingdao University, Qingdao, China"},{"name":"State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Eye Diseases, Eye Institute of Shandong First Medical University, Qingdao, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaowen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Xiamen University Affiliated Xiamen Eye Center, Eye Institute of Xiamen University, Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Fujian Engineering and Research Center of Eye Regenerative Medicine, School of Medicine, Xiamen University, Xiamen, Fujian, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Wei","sequence":"additional","affiliation":[{"name":"State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Eye Diseases, Eye Institute of Shandong First Medical University, Qingdao, China"},{"name":"School of Ophthalmology, Shandong First Medical University, Jinan, Shandong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huimin","family":"Yu","sequence":"additional","affiliation":[{"name":"Medical College, Qingdao University, Qingdao, China"},{"name":"State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Eye Diseases, Eye Institute of Shandong First Medical University, Qingdao, China"},{"name":"School of Ophthalmology, Shandong First Medical University, Jinan, Shandong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengqian","family":"Dou","sequence":"additional","affiliation":[{"name":"State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Eye Diseases, Eye Institute of Shandong First Medical University, Qingdao, China"},{"name":"School of Ophthalmology, Shandong First Medical University, Jinan, Shandong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Gao","sequence":"additional","affiliation":[{"name":"State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Eye Diseases, Eye Institute of Shandong First Medical University, Qingdao, China"},{"name":"School of Ophthalmology, Shandong First Medical University, Jinan, Shandong, China"},{"name":"School of Public Health, Shandong First Medical University, Jinan, Shandong, China"},{"name":"Eye Hospital of Shandong First Medical University, Eye Institute of Shandong First Medical University, Jinan, Shandong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"27","reference":[{"key":"bib1","doi-asserted-by":"publisher","first-page":"7","DOI":"10.5005\/jp-journals-10025-1002","article-title":"The epidemiology and etiology of keratoconus","volume":"1","author":"Gordon-Shaag","year":"2012","journal-title":"Int J Keratoconus Ectatic Corneal Dis"},{"key":"bib2","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1016\/j.clae.2010.04.006","article-title":"Keratoconus: a review","volume":"33","author":"Romero-Jim\u00e9nez","year":"2010","journal-title":"Contact Lens Anterio"},{"key":"bib3","doi-asserted-by":"publisher","first-page":"1441","DOI":"10.1097\/ICO.0b013e3182a0d014","article-title":"Prevalence of keratoconus in a population-based study in Shahroud","volume":"32","author":"Hashemi","year":"2013","journal-title":"Cornea"},{"key":"bib4","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1016\/j.ophtha.2011.07.057","article-title":"Long-term results of deep anterior lamellar versus penetrating keratoplasty","volume":"119","author":"Borderie","year":"2012","journal-title":"Ophthalmology"},{"key":"bib5","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1002\/1096-8628(20000828)93:5&lt;403::AID-AJMG11&gt;3.0.CO;2-A","article-title":"Genetic epidemiological study of keratoconus: evidence for major gene determination","volume":"93","author":"Wang","year":"2000","journal-title":"Am J Med Genet"},{"key":"bib6","doi-asserted-by":"publisher","first-page":"712","DOI":"10.3928\/1081597X-20230831-04","article-title":"Eye rubbing in Chinese patients with keratoconus: a multicenter analysis","volume":"39","author":"Guo","year":"2023","journal-title":"J Refract Surg"},{"key":"bib7","doi-asserted-by":"publisher","first-page":"2057","DOI":"10.1007\/s00417-021-05081-8","article-title":"Eye rubbing in the aetiology of keratoconus: a systematic review and meta-analysis","volume":"259","author":"Sahebjada","year":"2021","journal-title":"Graef Arch Clin Exp"},{"key":"bib8","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1038\/s41421-022-00397-z","article-title":"Single-cell atlas of keratoconus corneas revealed aberrant transcriptional signatures and implicated mechanical stretch as a trigger for keratoconus pathogenesis","volume":"8","author":"Dou","year":"2022","journal-title":"Cell Discov"},{"issue":"7350","key":"bib9","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1038\/nature10137","article-title":"Role of YAP\/TAZ in mechanotransduction","volume":"474","author":"Dupont","year":"2011","journal-title":"Nature"},{"issue":"8","key":"bib10","doi-asserted-by":"publisher","first-page":"107512","DOI":"10.1016\/j.jbc.2024.107512","article-title":"NEDD8 enhances Hippo signaling by mediating YAP1 neddylation","volume":"300","author":"Chen","year":"2024","journal-title":"J Biol Chem"},{"issue":"5558","key":"bib11","doi-asserted-by":"publisher","first-page":"1294","DOI":"10.1126\/science.1067765","article-title":"Cytoskeletal regulation by the Nedd8 ubiquitin-like protein modification pathway","volume":"295","author":"Kurz","year":"2002","journal-title":"Science"},{"issue":"17","key":"bib12","doi-asserted-by":"publisher","first-page":"E4101","DOI":"10.1073\/pnas.1719309115","article-title":"Neddylation mediates ventricular chamber maturation through repression of Hippo signaling","volume":"115","author":"Zou","year":"2018","journal-title":"Proc Natl Acad Sci USA"},{"key":"bib13","doi-asserted-by":"publisher","first-page":"272","DOI":"10.1016\/j.jtos.2015.04.006","article-title":"Cytokine expression in keratoconus and its corneal microenvironment: a systematic review","volume":"13","author":"Wisse","year":"2015","journal-title":"Ocul Surf"},{"key":"bib14","doi-asserted-by":"publisher","first-page":"654","DOI":"10.1016\/j.ophtha.2004.11.050","article-title":"Inflammatory molecules in the tears of patients with keratoconus","volume":"112","author":"Lema","year":"2005","journal-title":"Ophthalmology"},{"key":"bib15","first-page":"370","article-title":"Effects of vernal and allergic conjunctivitis on severity of keratoconus","volume":"6","author":"Cingu","year":"2013","journal-title":"Int J Ophthalmol"},{"key":"bib16","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1111\/cxo.12038","article-title":"Effects of eye rubbing on the levels of protease, protease activity and cytokines in tears: relevance in keratoconus","volume":"96","author":"Balasubramanian","year":"2013","journal-title":"Clin Exp Optom"},{"key":"bib17","doi-asserted-by":"publisher","first-page":"754","DOI":"10.1038\/s41419-021-04041-8","article-title":"Hippo-YAP\/MCP-1 mediated tubular maladaptive repair promote inflammation in renal failed recovery after ischemic AKI","volume":"12","author":"Zheng","year":"2021","journal-title":"Cell Death Dis"},{"key":"bib18","doi-asserted-by":"publisher","first-page":"1515","DOI":"10.1182\/blood-2010-03-272567","article-title":"MLN4924, a NEDD8-activating enzyme inhibitor, is active in diffuse large B-cell lymphoma models: rationale for treatment of NF-kappaB-dependent lymphoma","volume":"116","author":"Milhollen","year":"2010","journal-title":"Blood"},{"key":"bib19","doi-asserted-by":"publisher","first-page":"624","DOI":"10.1073\/pnas.1213819110","article-title":"Neddylation pathway regulates T-cell function by targeting an adaptor protein Shc and a protein kinase Erk signaling","volume":"110","author":"Jin","year":"2013","journal-title":"Proc Natl Acad Sci USA"},{"key":"bib20","doi-asserted-by":"publisher","first-page":"3687","DOI":"10.1091\/mbc.e16-05-0273","article-title":"Perturbation of neddylation-dependent NF-kappaB responses in the intestinal epithelium drives apoptosis and inhibits resolution of mucosal inflammation","volume":"27","author":"Ehrentraut","year":"2016","journal-title":"Mol Biol Cell"},{"issue":"6","key":"bib21","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1007\/s10142-024-01483-z","article-title":"Upregulation of Cullin1 neddylation promotes glycolysis and M1 polarization of macrophage via NF-kappaB p65 pathway in sepsis","volume":"24","author":"Qin","year":"2024","journal-title":"Funct Integr Genomics"},{"key":"bib22","first-page":"366","article-title":"Neddylation suppression by a macrophage membrane-coated nanoparticle promotes dual immunomodulatory repair of diabetic wounds","volume":"34","author":"Zeng","year":"2024","journal-title":"Bioact Mater"},{"key":"bib23","doi-asserted-by":"publisher","first-page":"110093","DOI":"10.1016\/j.exer.2024.110093","article-title":"CYR61\/CCN1: a novel mediator of redox response in corneal stromal cells of keratoconus.","volume":"248","author":"Liu","year":"2024","journal-title":"Exp Eye Res."},{"key":"bib24","doi-asserted-by":"publisher","first-page":"1484","DOI":"10.1038\/s41596-020-0292-x","article-title":"CellPhoneDB: inferring cell-cell communication from combined expression of multi-subunit ligand-receptor complexes","volume":"15","author":"Efremova","year":"2020","journal-title":"Nat Protoc"},{"key":"bib25","first-page":"1621","article-title":"Contralateral eye study of refractive, topographic and aberrometric outcomes after femtosecond assisted MyoRing implantation and DALK for management of keratoconus","volume":"11","author":"Yousif","year":"2018","journal-title":"Int J Ophthalmol"},{"key":"bib26","doi-asserted-by":"publisher","first-page":"294","DOI":"10.1111\/ceo.14047","article-title":"Femtosecond laser-assisted minimally invasive lamellar keratoplasty for the treatment of advanced keratoconus","volume":"50","author":"Gao","year":"2022","journal-title":"Clin Exp Ophthalmol"},{"key":"bib27","doi-asserted-by":"publisher","first-page":"1850","DOI":"10.1167\/iovs.02-0973","article-title":"Myofibroblast differentiation of normal human keratocytes and hTERT, extended-life human corneal fibroblasts","volume":"44","author":"Jester","year":"2003","journal-title":"Invest Ophthalmol Vis Sci"},{"issue":"5","key":"bib28","doi-asserted-by":"publisher","first-page":"e122943","DOI":"10.1172\/jci.insight.122943","article-title":"Platelet-derived beta2M regulates monocyte inflammatory responses","volume":"4","author":"Hilt","year":"2019","journal-title":"JCI Insight"},{"issue":"23","key":"bib29","doi-asserted-by":"publisher","first-page":"e149376","DOI":"10.1172\/jci.insight.149376","article-title":"ARPC1B binds WASP to control actin polymerization and curtail tonic signaling in B cells","volume":"6","author":"Leung","year":"2021","journal-title":"JCI Insight"},{"key":"bib30","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1097\/ACI.0000000000001099","article-title":"The immunopathology of keratoconus: tear film biomarkers and immune pathways","volume":"25","author":"Lombardo","year":"2025","journal-title":"Curr Opin Allergy Clin Immunol"},{"key":"bib31","doi-asserted-by":"publisher","first-page":"4587","DOI":"10.3390\/jcm14134587","article-title":"Keratoconus: the local manifestation of a systemic disease?","volume":"14","author":"Pederzolli","year":"2025","journal-title":"J Clin Med"},{"key":"bib32","doi-asserted-by":"publisher","first-page":"891763","DOI":"10.3389\/fcell.2022.891763","article-title":"The Ror-family receptors in development, tissue regeneration and age-related disease","volume":"10","author":"Endo","year":"2022","journal-title":"Front Cell Dev Biol"},{"key":"bib33","doi-asserted-by":"publisher","first-page":"1661","DOI":"10.1038\/s41375-025-02616-4","article-title":"Wnt5a induces ROR1 dependent NF-?B activation to enhance MMP-9 expression and invasiveness in chronic lymphocytic leukemia","volume":"39","author":"Hasan","year":"2025","journal-title":"Leukemia"},{"key":"bib34","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1111\/imm.13882","article-title":"The role of Wnt5a in inflammatory diseases","volume":"174","author":"Yu","year":"2025","journal-title":"Immunology"},{"key":"bib35","doi-asserted-by":"publisher","first-page":"567","DOI":"10.1007\/s00018-015-2076-y","article-title":"WNT-5A: signaling and functions in health and disease","volume":"73","author":"Kumawat","year":"2016","journal-title":"Cell Mol Life Sci"},{"key":"bib36","doi-asserted-by":"publisher","first-page":"1981","DOI":"10.3390\/cells13231981","article-title":"Role of protein tyrosine phosphatases in inflammatory bowel disease, celiac disease and diabetes: focus on the intestinal mucosa","volume":"13","author":"Bellomo","year":"2024","journal-title":"Cells"},{"key":"bib37","doi-asserted-by":"publisher","first-page":"598221","DOI":"10.3389\/fmolb.2020.598221","article-title":"ANTXR1 is a prognostic biomarker and correlates with stromal and immune cell infiltration in gastric cancer","volume":"7","author":"Huang","year":"2020","journal-title":"Front Mol Biosci"},{"key":"bib38","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1038\/s41420-023-01326-z","article-title":"Hepatic TNFRSF12A promotes bile acid-induced hepatocyte pyroptosis through NF?B\/Caspase-1\/GSDMD signaling in cholestasis","volume":"9","author":"Liao","year":"2023","journal-title":"Cell Death Discovery"},{"key":"bib39","article-title":"TNFSF10 drives hyperactive immune responses via NLRP3 inflammasome and endoplasmic reticulum stress in autoimmune and inflammatory diseases [Published online ahead of print January 16, 2026]","author":"Zhang","journal-title":"J Adv Res"},{"key":"bib40","doi-asserted-by":"publisher","first-page":"106694","DOI":"10.1016\/j.phrs.2023.106694","article-title":"The challenges and opportunities of av\u00df3-based therapeutics in cancer: from bench to clinical trials","volume":"189","author":"Gu","year":"2023","journal-title":"Pharmacol Res"},{"key":"bib41","doi-asserted-by":"publisher","first-page":"339","DOI":"10.3390\/cells13040339","article-title":"ICAMs in immunity, intercellular adhesion and communication","volume":"13","author":"Guerra-Espinosa","year":"2024","journal-title":"Cells"},{"key":"bib42","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1038\/s41420-023-01524-9","article-title":"The role of CXCL family members in different diseases","volume":"9","author":"Zhou","year":"2023","journal-title":"Cell Death Discovery"},{"issue":"4","key":"bib43","doi-asserted-by":"publisher","first-page":"102283","DOI":"10.1016\/j.isci.2021.102283","article-title":"Adhesion G protein-coupled receptor VLGR1\/ADGRV1 regulates cell spreading and migration by mechanosensing at focal adhesions","volume":"24","author":"Kusuluri","year":"2021","journal-title":"iScience"},{"key":"bib44","first-page":"151","article-title":"A corneal epithelial inhibitor of stromal cell collagenase synthesis identified as TGF-beta 2","volume":"36","author":"Strissel","year":"1995","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"bib45","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1016\/j.jtos.2023.06.014","article-title":"Transforming growth factor beta receptor 2 (Tgfbr2) deficiency in keratocytes results in corneal ectasia","volume":"29","author":"Wang","year":"2023","journal-title":"Ocular Surf"},{"key":"bib46","doi-asserted-by":"publisher","first-page":"697","DOI":"10.1097\/ICO.0000000000002283","article-title":"A case-control study of keratoconus risk factors","volume":"39","author":"Moran","year":"2020","journal-title":"Cornea"},{"key":"bib47","doi-asserted-by":"publisher","first-page":"2431","DOI":"10.1007\/s00417-020-04771-z","article-title":"Incorrect sleeping position and eye rubbing in patients with unilateral or highly asymmetric keratoconus: a case-control study","volume":"258","author":"Mazharian","year":"2020","journal-title":"Graefes Arch Clin Exp Ophthalmol"},{"key":"bib48","doi-asserted-by":"publisher","first-page":"999435","DOI":"10.3389\/fimmu.2022.999435","article-title":"Independent and interactive effects of eye rubbing and atopy on keratoconus","volume":"13","author":"Yang","year":"2022","journal-title":"Front Immunol"},{"key":"bib49","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1016\/S0039-6257(97)00119-7","article-title":"Keratoconus","volume":"42","author":"Rabinowitz","year":"1998","journal-title":"Surv Ophthalmol"},{"key":"bib50","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1016\/0039-6257(84)90094-8","article-title":"Keratoconus and related noninflammatory corneal thinning disorders","volume":"28","author":"Krachmer","year":"1984","journal-title":"Surv Ophthalmol"},{"issue":"30","key":"bib51","doi-asserted-by":"publisher","first-page":"e39067","DOI":"10.1097\/MD.0000000000039067","article-title":"Inflammation and keratoconus: a comprehensive bidirectional Mendelian randomization analysis","volume":"103","author":"Zhang","year":"2024","journal-title":"Medicine"},{"key":"bib52","doi-asserted-by":"publisher","first-page":"246","DOI":"10.1080\/09273948.2020.1780271","article-title":"Is keratoconus an inflammatory disease? The implication of inflammatory pathways","volume":"30","author":"Loh","year":"2022","journal-title":"Ocular Immunol Inflamm"},{"key":"bib53","doi-asserted-by":"publisher","first-page":"1350","DOI":"10.1136\/bjophthalmol-2021-318804","article-title":"Nationwide epidemiological approach to identify associations between keratoconus and immune-mediated diseases","volume":"106","author":"Claessens","year":"2022","journal-title":"Br J Ophthalmol"},{"key":"bib54","doi-asserted-by":"publisher","first-page":"4285268","DOI":"10.1155\/2018\/4285268","article-title":"Overexpression of tear inflammatory cytokines as additional finding in keratoconus patients and their first degree family members","volume":"2018","author":"Ionescu","year":"2018","journal-title":"Mediators Inflamm"},{"issue":"1","key":"bib55","doi-asserted-by":"publisher","first-page":"e16437","DOI":"10.1371\/journal.pone.0016437","article-title":"Subnormal cytokine profile in the tear fluid of keratoconus patients","volume":"6","author":"Jun","year":"2011","journal-title":"PLoS One"},{"key":"bib56","doi-asserted-by":"publisher","first-page":"5372","DOI":"10.1167\/iovs.16-19677","article-title":"Differential molecular expression of extracellular matrix and inflammatory genes at the corneal cone apex drives focal weakening in keratoconus","volume":"57","author":"Pahuja","year":"2016","journal-title":"Invest Ophth Vis Sci"},{"key":"bib57","doi-asserted-by":"publisher","first-page":"2326","DOI":"10.1128\/MCB.20.7.2326-2333.2000","article-title":"Nedd8 modification of cul-1 activates SCF(beta(TrCP))-dependent ubiquitination of IkappaBalpha","volume":"20","author":"Read","year":"2000","journal-title":"Mol Cell Biol"},{"key":"bib58","doi-asserted-by":"publisher","first-page":"23253","DOI":"10.1074\/jbc.M200967200","article-title":"The NEDD8 pathway is essential for SCF(beta -TrCP)-mediated ubiquitination and processing of the NF-kappa B precursor p105","volume":"277","author":"Amir","year":"2002","journal-title":"J Biol Chem"},{"key":"bib59","doi-asserted-by":"publisher","first-page":"528","DOI":"10.1038\/s41374-018-0175-8","article-title":"TRAF6 neddylation drives inflammatory arthritis by increasing NF-kappaB activation","volume":"99","author":"Liu","year":"2019","journal-title":"Lab Invest"},{"key":"bib60","doi-asserted-by":"publisher","first-page":"392","DOI":"10.4049\/jimmunol.1202041","article-title":"Central role for endothelial human deneddylase-1\/SENP8 in fine-tuning the vascular inflammatory response","volume":"190","author":"Ehrentraut","year":"2013","journal-title":"J Immunol"},{"issue":"13","key":"bib61","doi-asserted-by":"publisher","first-page":"E2766","DOI":"10.1073\/pnas.1618411114","article-title":"Inhibition of atherogenesis by the COP9 signalosome subunit 5 in vivo","volume":"114","author":"Asare","year":"2017","journal-title":"Proc Natl Acad Sci USA"},{"key":"bib62","doi-asserted-by":"publisher","first-page":"346","DOI":"10.1016\/j.tcb.2010.03.001","article-title":"Cell\/tissue-tropic functions of Wnt5a signaling in normal and cancer cells","volume":"20","author":"Nishita","year":"2010","journal-title":"Trends Cell Biol"},{"key":"bib63","doi-asserted-by":"publisher","first-page":"1146","DOI":"10.1097\/HEP.0000000000001064","article-title":"Integrative single-cell and spatial transcriptomic analyses identify a pathogenic cholangiocyte niche and TNFRSF12A as therapeutic target for biliary atresia","volume":"81","author":"Xiao","year":"2025","journal-title":"Hepatology"}],"container-title":["Investigative Ophthalmology &amp; Visual Science"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/iovs.arvojournals.org\/article.aspx?doi=10.1167\/iovs.67.6.14","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T21:32:14Z","timestamp":1791927134000},"score":1,"resource":{"primary":{"URL":"http:\/\/iovs.arvojournals.org\/article.aspx?doi=10.1167\/iovs.67.6.14"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,9]]},"references-count":63,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,6,1]]}},"URL":"https:\/\/doi.org\/10.1167\/iovs.67.6.14","relation":{},"ISSN":["1552-5783"],"issn-type":[{"value":"1552-5783","type":"print"}],"subject":[],"published":{"date-parts":[[2026,6,9]]}}}