{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T08:41:55Z","timestamp":1793090515987,"version":"4.5.0"},"reference-count":48,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2024,6,13]],"date-time":"2024-06-13T00:00:00Z","timestamp":1718236800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Allergy and Infectious Disease","award":["AI130790-03"],"award-info":[{"award-number":["AI130790-03"]}]},{"name":"National Institute of Allergy and Infectious Disease","award":["P20 GM 121299-04"],"award-info":[{"award-number":["P20 GM 121299-04"]}]},{"name":"National Institute of General Medical Sciences","award":["AI130790-03"],"award-info":[{"award-number":["AI130790-03"]}]},{"name":"National Institute of General Medical Sciences","award":["P20 GM 121299-04"],"award-info":[{"award-number":["P20 GM 121299-04"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Creatine transporter (CrT1) mediates cellular uptake of creatine (Cr), a nutrient pivotal in maintaining energy homeostasis in various tissues including intestinal epithelial cells (IECs). The impact of CrT1 deficiency on the pathogenesis of various psychiatric and neurological disorders has been extensively investigated. However, there are no studies on its regulation in IECs in health and disease. Current studies have determined differential expression of CrT1 along the length of the mammalian intestine and its dysregulation in inflammatory bowel disease (IBD)-associated inflammation and Adherent Invasive E. coli (AIEC) infection. CrT1 mRNA and protein levels in normal intestines and their alterations in inflammation and following AIEC infection were determined in vitro in model IECs (Caco-2\/IEC-6) and in vivo in SAMP1\/YitFc mice, a model of spontaneous ileitis resembling human IBD. CrT1 is differentially expressed in different regions of mammalian intestines with its highest expression in jejunum. In vitro, CrT1 function (Na+-dependent 14C-Cr uptake), expression and promoter activity significantly decreased following TNF\u03b1\/IL1\u03b2 treatments and AIEC infection. SAMP1 mice and ileal organoids generated from SAMP1 mice also showed decreased CrT1 mRNA and protein compared to AKR controls. Our studies suggest that Cr deficiency in IECs secondary to CrT1 dysregulation could be a key factor contributing to IBD pathogenesis.<\/jats:p>","DOI":"10.3390\/ijms25126537","type":"journal-article","created":{"date-parts":[[2024,6,14]],"date-time":"2024-06-14T08:52:10Z","timestamp":1718355130000},"page":"6537","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Intestinal Epithelial Creatine Transporter SLC6A8 Dysregulation in Inflammation and in Response to Adherent Invasive E. coli Infection"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-7908-4050","authenticated-orcid":false,"given":"Harshal","family":"Sawant","sequence":"first","affiliation":[{"name":"Department of Clinical and Translational Sciences, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25701, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajesh","family":"Selvaraj","sequence":"additional","affiliation":[{"name":"Department of Clinical and Translational Sciences, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25701, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6105-7818","authenticated-orcid":false,"given":"Prasath","family":"Manogaran","sequence":"additional","affiliation":[{"name":"Department of Clinical and Translational Sciences, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25701, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5792-1279","authenticated-orcid":false,"given":"Alip","family":"Borthakur","sequence":"additional","affiliation":[{"name":"Department of Clinical and Translational Sciences, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25701, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7247238","DOI":"10.1155\/2019\/7247238","article-title":"A Comprehensive Review and Update on the Pathogenesis of Inflammatory Bowel Disease","volume":"2019","author":"Guan","year":"2019","journal-title":"J. Immunol. Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1038\/nrgastro.2015.186","article-title":"Immunopathogenesis of IBD: Current state of the art","volume":"13","author":"Fiocchi","year":"2016","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_3","first-page":"75","article-title":"The Multifactorial Etiopathogeneses Interplay of Inflammatory Bowel Disease: An Overview","volume":"1","year":"2019","journal-title":"Gastrointest. 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