{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T02:48:29Z","timestamp":1781664509037,"version":"3.54.5"},"reference-count":45,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2022,6,1]],"date-time":"2022-06-01T00:00:00Z","timestamp":1654041600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2022,6,1]],"date-time":"2022-06-01T00:00:00Z","timestamp":1654041600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2022,6,1]],"date-time":"2022-06-01T00:00:00Z","timestamp":1654041600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2022,6,1]],"date-time":"2022-06-01T00:00:00Z","timestamp":1654041600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2022,6,1]],"date-time":"2022-06-01T00:00:00Z","timestamp":1654041600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2022,6,1]],"date-time":"2022-06-01T00:00:00Z","timestamp":1654041600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2022,6,1]],"date-time":"2022-06-01T00:00:00Z","timestamp":1654041600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Experimental Eye Research"],"published-print":{"date-parts":[[2022,6]]},"DOI":"10.1016\/j.exer.2022.109070","type":"journal-article","created":{"date-parts":[[2022,4,9]],"date-time":"2022-04-09T10:41:31Z","timestamp":1649500891000},"page":"109070","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":6,"special_numbering":"C","title":["Sprouty and Spred temporally regulate ERK1\/2-signaling to suppress TGF\u03b2-induced lens EMT"],"prefix":"10.1016","volume":"219","author":[{"given":"Guannan","family":"Zhao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela Y.","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John E.J.","family":"Rasko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles G.","family":"Bailey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5492-9200","authenticated-orcid":false,"given":"Frank J.","family":"Lovicu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"6","key":"10.1016\/j.exer.2022.109070_bib1","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1016\/j.semcdb.2006.10.007","article-title":"Sef and Sprouty expression in the developing ocular lens: implications for regulating lens cell proliferation and differentiation","volume":"17","author":"Boros","year":"2006","journal-title":"Semin. Cell Dev. Biol."},{"issue":"7","key":"10.1016\/j.exer.2022.109070_bib2","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1091\/mbc.e16-12-0865","article-title":"Dual function of TGF\u03b2 in lens epithelial cell fate: implications for secondary cataract","volume":"28","author":"Boswell","year":"2017","journal-title":"Mol. Biol. Cell"},{"issue":"2","key":"10.1016\/j.exer.2022.109070_bib3","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0056280","article-title":"miR-21 promotes fibrogenic epithelial-to-mesenchymal transition of epicardial mesothelial cells involving programmed cell death 4 and sprouty-1","volume":"8","author":"Br\u00f8nnum","year":"2013","journal-title":"PLoS One"},{"issue":"3","key":"10.1016\/j.exer.2022.109070_bib4","doi-asserted-by":"crossref","first-page":"1631","DOI":"10.1007\/s11010-020-04034-9","article-title":"Moderate oxidative stress promotes epithelial-mesenchymal transition in the lens epithelial cells via the TGF-beta\/Smad and Wnt\/beta-catenin pathways","volume":"476","author":"Chen","year":"2021","journal-title":"Mol. Cell. Biochem."},{"issue":"6","key":"10.1016\/j.exer.2022.109070_bib5","doi-asserted-by":"crossref","first-page":"2708","DOI":"10.1167\/iovs.06-0639","article-title":"Transforming growth factor-\u03b21 represses E-cadherin production via slug expression in lens epithelial cells","volume":"48","author":"Choi","year":"2007","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"issue":"2","key":"10.1016\/j.exer.2022.109070_bib6","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/j.exer.2008.07.018","article-title":"TGFbeta promotes Wnt expression during cataract development","volume":"88","author":"Chong","year":"2009","journal-title":"Exp. Eye Res."},{"key":"10.1016\/j.exer.2022.109070_bib7","first-page":"1181","article-title":"Oligonucleotide microarray analysis of human lens epithelial cells: TGFbeta regulated gene expression","volume":"13","author":"Dawes","year":"2007","journal-title":"Mol. Vis."},{"issue":"1\u20132","key":"10.1016\/j.exer.2022.109070_bib8","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1159\/000084508","article-title":"Transforming growth factor-beta-induced epithelial-mesenchymal transition in the lens: a model for cataract formation","volume":"179","author":"de Iongh","year":"2005","journal-title":"Cells Tissues Organs"},{"issue":"6958","key":"10.1016\/j.exer.2022.109070_bib9","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1038\/nature02006","article-title":"Smad-dependent and Smad-independent pathways in TGF-\u03b2 family signalling","volume":"425","author":"Derynck","year":"2003","journal-title":"Nature"},{"key":"10.1016\/j.exer.2022.109070_bib10","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1002\/jcp.21078","article-title":"Sprouty2 downregulation plays a pivotal role in mediating crosstalk between TGF-beta1 signaling and EGF as well as FGF receptor tyrosine kinase-ERK pathways in mesenchymal cells","volume":"212","author":"Ding","year":"2007","journal-title":"J. Cell. Physiol."},{"issue":"12","key":"10.1016\/j.exer.2022.109070_bib11","doi-asserted-by":"crossref","first-page":"885","DOI":"10.3109\/02713689409015091","article-title":"TGF-\u03b21 induces lens cells to accumulate \u03b1-smooth muscle actin, a marker for subcapsular cataracts","volume":"13","author":"Hales","year":"1994","journal-title":"Curr. Eye Res."},{"issue":"8","key":"10.1016\/j.exer.2022.109070_bib12","first-page":"1709","article-title":"Cataract induction in lenses cultured with transforming growth factor-beta","volume":"36","author":"Hales","year":"1995","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"issue":"1","key":"10.1016\/j.exer.2022.109070_bib13","doi-asserted-by":"crossref","first-page":"16490","DOI":"10.1038\/s41598-020-73752-3","article-title":"Spred2-deficiency enhances the proliferation of lung epithelial cells and alleviates pulmonary fibrosis induced by bleomycin","volume":"10","author":"Kawara","year":"2020","journal-title":"Sci. Rep."},{"issue":"5","key":"10.1016\/j.exer.2022.109070_bib14","doi-asserted-by":"crossref","first-page":"1525","DOI":"10.1111\/cas.13999","article-title":"The Sprouty\/Spred family as tumor suppressors: coming of age","volume":"110","author":"Kawazoe","year":"2019","journal-title":"Cancer Sci."},{"issue":"6","key":"10.1016\/j.exer.2022.109070_bib15","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1038\/nrm1400","article-title":"Modulation of signalling by Sprouty: a developing story","volume":"5","author":"Kim","year":"2004","journal-title":"Nat. Rev. Mol. Cell Biol."},{"issue":"7","key":"10.1016\/j.exer.2022.109070_bib16","doi-asserted-by":"crossref","first-page":"2001","DOI":"10.1016\/j.ajpath.2014.03.013","article-title":"Matrix metalloproteinase-9\u2013null mice are resistant to TGF-\u03b2\u2013induced anterior subcapsular cataract formation","volume":"184","author":"Korol","year":"2014","journal-title":"Am. J. Pathol."},{"issue":"9","key":"10.1016\/j.exer.2022.109070_bib17","doi-asserted-by":"crossref","first-page":"6887","DOI":"10.1167\/iovs.11-7531","article-title":"Spry1 and Spry2 are necessary for lens vesicle separation and corneal differentiation","volume":"52","author":"Kuracha","year":"2011","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"issue":"23","key":"10.1016\/j.exer.2022.109070_bib18","doi-asserted-by":"crossref","first-page":"4397","DOI":"10.1007\/s00018-016-2297-8","article-title":"Negative feedback regulation of the ERK1\/2 MAPK pathway","volume":"73","author":"Lake","year":"2016","journal-title":"Cell. Mol. Life Sci. : CMLS"},{"issue":"2","key":"10.1016\/j.exer.2022.109070_bib19","first-page":"388","article-title":"Induction of cataract-like changes in rat lens epithelial explants by transforming growth factor beta","volume":"35","author":"Liu","year":"1994","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"issue":"1","key":"10.1016\/j.exer.2022.109070_bib20","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ydbio.2005.01.020","article-title":"Growth factor regulation of lens development","volume":"280","author":"Lovicu","year":"2005","journal-title":"Dev. Biol."},{"key":"10.1016\/j.exer.2022.109070_bib21","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.exer.2015.02.004","article-title":"Fibrosis in the lens. Sprouty regulation of TGF\u03b2-signaling prevents lens EMT leading to cataract","volume":"142","author":"Lovicu","year":"2016","journal-title":"Exp. Eye Res."},{"issue":"2\u20133","key":"10.1016\/j.exer.2022.109070_bib22","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1007\/s10555-014-9497-1","article-title":"The developing story of Sprouty and cancer","volume":"33","author":"Masoumi-Moghaddam","year":"2014","journal-title":"Cancer Metastasis Rev."},{"issue":"5","key":"10.1016\/j.exer.2022.109070_bib23","first-page":"1122","article-title":"Alpha-smooth muscle actin expression in cultured lens epithelial cells","volume":"41","author":"Nagamoto","year":"2000","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"10.1016\/j.exer.2022.109070_bib24","doi-asserted-by":"crossref","DOI":"10.5402\/2012\/381428","article-title":"The dual role of TGF\u03b2 in human cancer: from tumor suppression to cancer metastasis","author":"Neel","year":"2012","journal-title":"ISRN Molecular Biology"},{"key":"10.1016\/j.exer.2022.109070_bib25","first-page":"5","article-title":"Gene expressing profiling reveals novel TGFbeta targets in adult lung fibroblasts","volume":"30","author":"Renzoni","year":"2004","journal-title":"Respir. Res."},{"issue":"2","key":"10.1016\/j.exer.2022.109070_bib26","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.phrs.2012.04.005","article-title":"ERK1\/2 MAP kinases: structure, function, and regulation","volume":"66","author":"Roskoski","year":"2012","journal-title":"Pharmacol. Res."},{"issue":"2","key":"10.1016\/j.exer.2022.109070_bib27","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1111\/j.1432-0436.1990.tb00437.x","article-title":"Appearance of alpha-smooth muscle actin in human eye lens cells of anterior capsular cataract and in cultured bovine lens-forming cells","volume":"43","author":"Schmitt-Gr\u00e4ff","year":"1990","journal-title":"Differentiation"},{"issue":"2","key":"10.1016\/j.exer.2022.109070_bib28","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.ydbio.2015.09.005","article-title":"Sprouty gain of function disrupts lens cellular processes and growth by restricting RTK signaling","volume":"406","author":"Shin","year":"2015","journal-title":"Dev. Biol."},{"issue":"5","key":"10.1016\/j.exer.2022.109070_bib29","doi-asserted-by":"crossref","first-page":"861","DOI":"10.2119\/molmed.2012.00111","article-title":"Sprouty is a negative regulator of transforming growth factor \u03b2-induced epithelial-to-mesenchymal transition and cataract","volume":"18","author":"Shin","year":"2012","journal-title":"Mol. Med."},{"issue":"1","key":"10.1016\/j.exer.2022.109070_bib30","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/j.molcel.2010.02.020","article-title":"ERK2 but not ERK1 induces epithelial-to-mesenchymal transformation via DEF motif-dependent signaling events","volume":"38","author":"Shin","year":"2010","journal-title":"Mol. Cell"},{"key":"10.1016\/j.exer.2022.109070_bib31","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.preteyeres.2017.08.001","article-title":"Myofibroblast transdifferentiation: the dark force in ocular wound healing and fibrosis","volume":"60","author":"Shu","year":"2017","journal-title":"Prog. Retin. Eye Res."},{"key":"10.1016\/j.exer.2022.109070_bib32","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.exer.2018.09.021","article-title":"ERK1\/2-mediated EGFR-signaling is required for TGF\u03b2-induced lens epithelial-mesenchymal transition","volume":"178","author":"Shu","year":"2019","journal-title":"Exp. Eye Res."},{"key":"10.1016\/j.exer.2022.109070_bib33","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.exer.2018.09.019","article-title":"Spred negatively regulates lens growth by modulating epithelial cell proliferation and fiber differentiation","volume":"178","author":"Susanto","year":"2019","journal-title":"Exp. Eye Res."},{"issue":"7","key":"10.1016\/j.exer.2022.109070_bib34","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0159275","article-title":"Sprouty2 suppresses epithelial-mesenchymal transition of human lens epithelial cells through blockade of Smad2 and ERK1\/2 pathways","volume":"11","author":"Tan","year":"2016","journal-title":"PLoS One"},{"key":"10.1016\/j.exer.2022.109070_bib35","article-title":"E-cadherin\/\u03b2-catenin complex and the epithelial barrier","author":"Tian","year":"2011","journal-title":"J. Biomed. Biotechnol."},{"issue":"1","key":"10.1016\/j.exer.2022.109070_bib36","doi-asserted-by":"crossref","first-page":"7274","DOI":"10.1038\/s41598-017-07619-5","article-title":"Roles of TGF\u03b2 and FGF signals during growth and differentiation of mouse lens epithelial cell in vitro","volume":"7","author":"Wang","year":"2017","journal-title":"Sci. Rep."},{"issue":"1","key":"10.1016\/j.exer.2022.109070_bib37","first-page":"174","article-title":"Spred2 inhibits epithelial-mesenchymal transition of colorectal cancer cells by impairing ERK signaling","volume":"44","author":"Wang","year":"2020","journal-title":"Oncol. Rep."},{"issue":"2","key":"10.1016\/j.exer.2022.109070_bib45","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.preteyeres.2009.12.001","article-title":"Development and use of the lens epithelial explant system to study lens differentiation and cataractogenesis","volume":"29","author":"West-Mays","year":"2010","journal-title":"Prog. Retin. Eye Res."},{"issue":"8","key":"10.1016\/j.exer.2022.109070_bib38","doi-asserted-by":"crossref","first-page":"992","DOI":"10.1046\/j.1365-2168.2000.01513.x","article-title":"E-cadherin-catenin cell-cell adhesion complex and human cancer","volume":"87","author":"Wijnhoven","year":"2000","journal-title":"Br. J. Surg."},{"key":"10.1016\/j.exer.2022.109070_bib39","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.exer.2017.03.012","article-title":"ERK1\/2 signaling is required for the initiation but not progression of TGF\u03b2-induced lens epithelial to mesenchymal transition (EMT)","volume":"159","author":"Wojciechowski","year":"2017","journal-title":"Exp. Eye Res."},{"key":"10.1016\/j.exer.2022.109070_bib40","first-page":"29","article-title":"miR-19 promotes cell proliferation, invasion, migration, and EMT by inhibiting SPRED2-mediated autophagy in osteosarcoma cells","author":"Xie","year":"2020","journal-title":"Cell Transplant."},{"issue":"2","key":"10.1016\/j.exer.2022.109070_bib41","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1038\/cr.2009.5","article-title":"TGF-beta-induced epithelial to mesenchymal transition","volume":"19","author":"Xu","year":"2009","journal-title":"Cell Res."},{"issue":"24","key":"10.1016\/j.exer.2022.109070_bib42","doi-asserted-by":"crossref","first-page":"3151","DOI":"10.1038\/onc.2015.365","article-title":"Atypical role of sprouty in colorectal cancer: sprouty repression inhibits epithelial-mesenchymal transition","volume":"35","author":"Zhang","year":"2016","journal-title":"Oncogene"},{"key":"10.1016\/j.exer.2022.109070_bib43","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.exer.2018.02.025","article-title":"Negative regulation of lens fiber cell differentiation by RTK antagonists Spry and Spred","volume":"170","author":"Zhao","year":"2018","journal-title":"Exp. Eye Res."},{"key":"10.1016\/j.exer.2022.109070_bib44","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.exer.2015.01.001","article-title":"Negative regulation of TGF\u03b2-induced lens epithelial to mesenchymal transition (EMT) by RTK antagonists","volume":"132","author":"Zhao","year":"2015","journal-title":"Exp. Eye Res."}],"container-title":["Experimental Eye Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0014483522001506?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0014483522001506?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,16]],"date-time":"2025-09-16T05:21:25Z","timestamp":1758000085000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0014483522001506"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6]]},"references-count":45,"alternative-id":["S0014483522001506"],"URL":"https:\/\/doi.org\/10.1016\/j.exer.2022.109070","relation":{},"ISSN":["0014-4835"],"issn-type":[{"value":"0014-4835","type":"print"}],"subject":[],"published":{"date-parts":[[2022,6]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Sprouty and Spred temporally regulate ERK1\/2-signaling to suppress TGF\u03b2-induced lens EMT","name":"articletitle","label":"Article Title"},{"value":"Experimental Eye Research","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.exer.2022.109070","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"Crown Copyright \u00a9 2022 Published by Elsevier Ltd. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"109070"}}