{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T15:59:46Z","timestamp":1787673586404,"version":"build-2736575974"},"reference-count":55,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2018,12,4]],"date-time":"2018-12-04T00:00:00Z","timestamp":1543881600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100010032","name":"Health and Family Planning Commission of Sichuan Province","doi-asserted-by":"publisher","award":["20184Y0337"],"award-info":[{"award-number":["20184Y0337"]}],"id":[{"id":"10.13039\/501100010032","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81630039"],"award-info":[{"award-number":["81630039"]}],"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":["81700787"],"award-info":[{"award-number":["81700787"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2019,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Intestinal villus atrophy is a major complication of total parenteral nutrition (TPN). Our previous study revealed that TPN\u2010induced villus atrophy is accompanied by elevated expression of CUGBP, Elav\u2010like family member 1 (CELF1); however, its mechanism of action has not been fully understood. Herein, we report a pivotal role of CELF1\/p53 axis, which induces a sustained antiproliferative signal, leading to suppressed proliferation of intestinal epithelial cells (IECs). By using a rat model of TPN, we found synchronous upregulation of CELF1 and p53 in jejunum mucosa, accompanied by a 51% decrease in crypt cell proliferation rate. By using HCT\u2010116 cells as an IEC model\n                    <jats:italic>in vitro<\/jats:italic>\n                    , we found that the expression of CELF1 altered dynamically in parallel to proliferation rate, suggesting a self\u2010adaptive expression pattern in IECs\n                    <jats:italic>in vitro<\/jats:italic>\n                    . Furthermore, ectopic overexpression of CELF1 elicited a significant antiproliferative effect in HCT\u2010116, Caco\u20102, and IEC\u20106 cells, whereas knockdown of CELF1 elicited a significant proproliferative effect. Moreover, cell\u2010cycle assay revealed that ectopic overexpression of CELF1 induced sustained G2 arrest and G1 arrest in HCT\u2010116 and IEC\u20106 cells, respectively, which could be abolished by p53 silencing. Mechanistically, polysomal profiling and nascent protein analysis revealed that regulation of p53 by CELF1 was mediated through accelerating its protein translation in polysomes. Taken together, our findings revealed a sustained suppression of IEC proliferation evoked by CELF1\/p53 axis, which may be a potential therapeutic target for the treatment of TPN\u2010induced villus atrophy.\u2014Yan, J.\u2010K., Zhang, T., Dai, L.\u2010N., Gu, B.\u2010L., Zhu, J., Yan, W.\u2010H., Cai, W., Wang, Y. CELF1\/p53 axis: a sustained antiproliferative signal leading to villus atrophy under total parenteral nutrition. FASEB J. 33, 3378\u20133391 (2019).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201801695r","type":"journal-article","created":{"date-parts":[[2018,12,4]],"date-time":"2018-12-04T22:01:56Z","timestamp":1543960916000},"page":"3378-3391","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["CELF1\/p53 axis: a sustained antiproliferative signal leading to villus atrophy under total parenteral nutrition"],"prefix":"10.1096","volume":"33","author":[{"given":"Jun-Kai","family":"Yan","sequence":"first","affiliation":[{"name":"Xin Hua Hospital School of Medicine Shanghai Jiao Tong University  Shanghai China"},{"name":"Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition Shanghai Institute for Pediatric Research  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian","family":"Zhang","sequence":"additional","affiliation":[{"name":"Xin Hua Hospital School of Medicine Shanghai Jiao Tong University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li-Na","family":"Dai","sequence":"additional","affiliation":[{"name":"Xin Hua Hospital School of Medicine Shanghai Jiao Tong University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bei-Lin","family":"Gu","sequence":"additional","affiliation":[{"name":"Xin Hua Hospital School of Medicine Shanghai Jiao Tong University  Shanghai China"},{"name":"Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition Shanghai Institute for Pediatric Research  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Zhu","sequence":"additional","affiliation":[{"name":"Xin Hua Hospital School of Medicine Shanghai Jiao Tong University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-Hui","family":"Yan","sequence":"additional","affiliation":[{"name":"Xin Hua Hospital School of Medicine Shanghai Jiao Tong University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Cai","sequence":"additional","affiliation":[{"name":"Xin Hua Hospital School of Medicine Shanghai Jiao Tong University  Shanghai China"},{"name":"Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition Shanghai Institute for Pediatric Research  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Wang","sequence":"additional","affiliation":[{"name":"Xin Hua Hospital School of Medicine Shanghai Jiao Tong University  Shanghai China"},{"name":"Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition Shanghai Institute for Pediatric Research  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,12,4]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.scr.2014.12.002"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1234852"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-642-24716-3_14"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.13-238311"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.4161\/19490976.2014.972238"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2008.02.014"},{"key":"e_1_2_8_8_1","unstructured":"Timmons J. Chang E. T. Wang J. Y. andRao J. N.(2012)Polyamines and gut mucosal homeostasis.J. Gastrointest. Dig. Syst. 2 001 (Suppl 7)"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00726-007-0518-z"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.14814\/phy2.12858"},{"key":"e_1_2_8_11_1","doi-asserted-by":"crossref","first-page":"3308","DOI":"10.1091\/mbc.e14-03-0853","article-title":"RNA-binding protein HuR promotes growth of small intestinal mucosa by activating the Wnt signaling pathway","volume":"25","author":"Liu L.","year":"2014","journal-title":"Mol. Biol. Cell"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2014.07.006"},{"key":"e_1_2_8_13_1","doi-asserted-by":"crossref","unstructured":"Belcheva A.(2017)MicroRNAs at the epicenter of intestinal homeostasis.Bioessays39","DOI":"10.1002\/bies.201600200"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00280.2011"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0007114510001613"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2008.162719"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep18174"},{"key":"e_1_2_8_18_1","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1091\/mbc.e11-05-0456","article-title":"miR-503 represses CUG-binding protein 1 translation by recruiting CUGBP1 mRNA to processing bodies","volume":"23","author":"Cui Y. H.","year":"2012","journal-title":"Mol. Biol. Cell"},{"key":"e_1_2_8_19_1","doi-asserted-by":"crossref","unstructured":"Wang J. Y. Xiao L. andWang J. Y.(2017)Posttranscriptional regulation of intestinal epithelial integrity by noncoding RNAs.Wiley Interdiscip. Rev. RNA8","DOI":"10.1002\/wrna.1399"},{"key":"e_1_2_8_20_1","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.molcel.2008.01.005","article-title":"GU-rich RNA: expanding CUGBP1 function. broadening mRNA turnover","volume":"29","author":"Kim H. H.","year":"2008","journal-title":"Mol. Cell"},{"key":"e_1_2_8_21_1","first-page":"385","article-title":"Molecular basis of myotonic dystrophy: expansion of a trinucleotide (CTG) repeat at the 3\u2032 end of a transcript encoding a protein kinase family member","volume":"69","author":"Brook J. D.","year":"1992","journal-title":"Cell"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00112.2015"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E14-11-1500"},{"key":"e_1_2_8_24_1","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1177\/0148607116677048","article-title":"Choline protects against intestinal failure-associated liver disease in parenteral nutrition-fed immature rats","volume":"42","author":"Zhu J.","year":"2016","journal-title":"JPEN J. Parenter. Enteral. Nutr."},{"key":"e_1_2_8_25_1","doi-asserted-by":"crossref","first-page":"1581","DOI":"10.1159\/000447860","article-title":"Soybean oil-based lipid emulsion increases intestinal permeability of lipopolysaccharide in caco-2 cells by downregulation of P-glycoprotein via ERK-FOXO 3a pathway","volume":"39","author":"Yan J. K.","year":"2016","journal-title":"Cell. Physiol. Biochem."},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)65545-9"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.13430"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1159\/000458430"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clnu.2009.04.002"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.25500"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2006.091108"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00030.2010"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00142.2011"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.14-269480"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.4161\/rna.23315"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/1759-7714.12268"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2007.07.021"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2012.02.007"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M605701200"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2017.01.049"},{"key":"e_1_2_8_41_1","doi-asserted-by":"crossref","first-page":"16344","DOI":"10.1038\/srep16344","article-title":"Divalent metal-ion transporter 1 is decreased in intestinal epithelial cells and contributes to the anemia in inflammatory bowel disease","volume":"5","author":"Wu W.","year":"2015","journal-title":"Sci Rep."},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2013.07.001"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1142\/S0192415X15500469"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.282.5393.1497"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.2001.281.1.G37"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1999.276.3.C684"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.4161\/rna.7056"},{"key":"e_1_2_8_48_1","doi-asserted-by":"crossref","first-page":"3055","DOI":"10.1091\/mbc.e11-01-0069","article-title":"Regulation of cyclin-dependent kinase 4 translation through CUGbinding protein 1 and microRNA-222 by polyamines","volume":"22","author":"Xiao L.","year":"2011","journal-title":"Mol. Biol. Cell"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7600052"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20120112"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00037.2008"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00421-15"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.5858\/arpa.2012-0354-OA"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1080\/1745039X.2011.594352"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.01009-06"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1002\/cbin.10356"}],"container-title":["The FASEB Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.201801695R","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1096\/fj.201801695R","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.201801695R","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T17:48:20Z","timestamp":1761673700000},"score":1,"resource":{"primary":{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/10.1096\/fj.201801695R"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,12,4]]},"references-count":55,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2019,3]]}},"alternative-id":["10.1096\/fj.201801695R"],"URL":"https:\/\/doi.org\/10.1096\/fj.201801695r","archive":["Portico"],"relation":{},"ISSN":["0892-6638","1530-6860"],"issn-type":[{"value":"0892-6638","type":"print"},{"value":"1530-6860","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,12,4]]},"assertion":[{"value":"2018-08-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-10-09","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-12-04","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}