{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T15:29:05Z","timestamp":1788449345387,"version":"build-2803163510"},"reference-count":48,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2021,3,25]],"date-time":"2021-03-25T00:00:00Z","timestamp":1616630400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100012807","name":"Midwestern University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012807","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cell Biology International"],"published-print":{"date-parts":[[2021,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>There is a growing controversy about the role of the epithelial to mesenchymal transition (EMT) in the fibrosis associated with chronic disease. Recent studies suggest that it is not the EMT transcriptional program but differentiation of progenitor cells, response to chronic inflammation, or some combination of both which cause the appearance of fibroblasts and the production of the extracellular matrix. To address this issue, we study the EMT process in the zebrafish keratocytes which migrate from primary explants of epithelial tissue as these cells are both terminally differentiated and able to divide. To firmly place this EMT process in the context of other systems, we first demonstrate that the zebrafish keratocyte EMT process involves nuclear accumulation of twist and snail\/slug transcription factors as part of a TGF\u03b2R\u2010mediated EMT process. As assessed by the expression and localization of EMT transcription factors, the zebrafish keratocyte EMT process is reversed by the addition of Rho\u2010activated kinase (ROCK) in combination with TGF\u03b2R inhibitors. The complete cycle of EMT to MET observed in this system links these in vitro results more closely to the process of wound healing in vivo. However, the absence of observable activation of EMT transcription factors when keratocytes are cultured on compliant substrata in a TGF\u03b21\u2010containing medium suggests that ROCK signaling, initiated by tension within the sheet, is an essential contributor to the EMT process. Most importantly, the requirement for ROCK activation by culturing on noncompliant substrata suggests that EMT in these terminally differentiated cells would not occur in vivo.<\/jats:p>","DOI":"10.1002\/cbin.11587","type":"journal-article","created":{"date-parts":[[2021,3,12]],"date-time":"2021-03-12T10:33:18Z","timestamp":1615545198000},"page":"1288-1295","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Dual inhibition of TGF\u03b2R and ROCK reverses the epithelial to mesenchymal transition in collectively migrating zebrafish keratocytes"],"prefix":"10.1002","volume":"45","author":[{"given":"Agnes S.","family":"Pascual","sequence":"first","affiliation":[{"name":"Biomedical Sciences Program, College of Graduate Studies Midwestern University Glendale Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose L.","family":"Rapanan","sequence":"additional","affiliation":[{"name":"Arizona College of Osteopathic Medicine Midwestern University Glendale Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chandana K.","family":"Uppalapati","sequence":"additional","affiliation":[{"name":"Department of Microbiology &amp; Immunology, College of Graduate Studies Midwestern University Glendale Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimbal E.","family":"Cooper","sequence":"additional","affiliation":[{"name":"Biomedical Sciences Program, College of Graduate Studies Midwestern University Glendale Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5093-6315","authenticated-orcid":false,"given":"Kathryn J.","family":"Leyva","sequence":"additional","affiliation":[{"name":"Department of Microbiology &amp; Immunology, College of Graduate Studies Midwestern University Glendale Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6100-9605","authenticated-orcid":false,"given":"Elizabeth E.","family":"Hull","sequence":"additional","affiliation":[{"name":"Biomedical Sciences Program, College of Graduate Studies Midwestern University Glendale Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,3,25]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e12-03-0172"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200507111"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/thoraxjnl-2013-204608"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0169(1998)41:2<126::AID-CM4>3.0.CO;2-C"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.12.1.27"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2536483100"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmbbm.2012.11.003"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellbi.2007.04.006"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2121-10-94"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3495(91)82027-6"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/2953727"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-13091-8"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2019.00388"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2613.2011.00775.x"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2013.04.018"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1359-6101(99)00037-4"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.24561"},{"key":"e_1_2_8_19_1","first-page":"517","article-title":"EMT and interstitial lung disease: A mysterious relationship","volume":"18","author":"Kage H.","year":"2012","journal-title":"Current Opinion in Pulmonary Medicine"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI39104"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M403960200"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.2119\/molmed.2016.00041"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI44595"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/362167a0"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.110.22.2833"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi300758e"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells4040631"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbm.a.34068"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2013.03.036"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejcb.2010.09.009"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-011-1219-1"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jim.2010.09.008"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2014.06.011"},{"key":"e_1_2_8_34_1","first-page":"e52489","article-title":"Zebrafish keratocyte explants to study collective cell migration and reepithelialization in cutaneous wound healing","author":"Rapanan J. L.","year":"2015","journal-title":"Journal of Visualized Experiments"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2013.16"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-016-2464-0"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1042\/CBI20110063"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.098087"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/40187"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E04-08-0658"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2010.233460"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijsolstr.2010.04.018"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2013.02.007"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2807"},{"key":"e_1_2_8_45_1","first-page":"3312","article-title":"Type 2 epithelial mesenchymal transition in vivo: Truth or pitfalls?","volume":"125","author":"Xu X. F.","year":"2012","journal-title":"Chinese Medical Journal (England)"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-04-3480"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.111614398"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.3892\/ijmm.2013.1396"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1002\/adem.201180057"}],"container-title":["Cell Biology International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cbin.11587","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cbin.11587","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cbin.11587","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,1]],"date-time":"2023-09-01T22:15:51Z","timestamp":1693606551000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cbin.11587"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,25]]},"references-count":48,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2021,6]]}},"alternative-id":["10.1002\/cbin.11587"],"URL":"https:\/\/doi.org\/10.1002\/cbin.11587","archive":["Portico"],"relation":{},"ISSN":["1065-6995","1095-8355"],"issn-type":[{"value":"1065-6995","type":"print"},{"value":"1095-8355","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,25]]},"assertion":[{"value":"2020-08-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-02-07","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-03-25","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}