{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T05:24:13Z","timestamp":1791350653531,"version":"4.3.1"},"reference-count":35,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2017,5,19]],"date-time":"2017-05-19T00:00:00Z","timestamp":1495152000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004622","name":"KWF Kankerbestrijding","doi-asserted-by":"publisher","award":["UM 2013\u20106075"],"award-info":[{"award-number":["UM 2013\u20106075"]}],"id":[{"id":"10.13039\/501100004622","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neurogastroenterology Motil"],"published-print":{"date-parts":[[2017,9]]},"abstract":"Abstract<\/jats:title>\n \n Background<\/jats:title>\n \n Promoter methylation of\n N\u2010myc Downstream\u2010Regulated Gene 4<\/jats:italic>\n (\n NDRG<\/jats:styled-content>\n 4) in fecal\n DNA<\/jats:styled-content>\n is an established early detection marker for colorectal cancer (\n CRC<\/jats:styled-content>\n ). Despite its connection to\n CRC<\/jats:styled-content>\n ,\n NDRG<\/jats:styled-content>\n 4 is predominantly studied in brain and heart, with little to no knowledge about its expression or role in other organs. In this study, we aimed to determine the whole\u2010body expression of\n NDRG<\/jats:styled-content>\n 4, with a focus on the intestinal tract.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n We investigated\n NDRG<\/jats:styled-content>\n 4 expression throughout the body by immunohistochemistry, Western Blotting and\n \n in situ\n mRNA<\/jats:styled-content>\n <\/jats:italic>\n hybridization using tissues from\n \n NDRG<\/jats:styled-content>\n 4\n <\/jats:italic>\n wild\u2010type, heterozygous and knockout mice and humans. In addition, we explored cell\u2010specific expression of\n NDRG<\/jats:styled-content>\n 4 in murine whole\u2010mount gut preparations using immunofluorescence and confocal microscopy.\n <\/jats:p>\n <\/jats:sec>\n \n Key Results<\/jats:title>\n \n NDRG<\/jats:styled-content>\n 4 is specifically expressed within nervous system structures throughout the body. In the intestinal tract of both mouse and man,\n NDRG<\/jats:styled-content>\n 4 immunoreactivity was restricted to the enteric nervous system (\n ENS<\/jats:styled-content>\n ), where it labeled cell bodies of the myenteric and submucosal plexuses and interconnecting nerve fibers. More precisely,\n NDRG<\/jats:styled-content>\n 4 expression was limited to neurons, as\n NDRG<\/jats:styled-content>\n 4 always co\u2010localized with HuC\/D (pan\u2010neuronal marker) but never with\n GFAP<\/jats:styled-content>\n (an enteric glial cell marker). Furthermore,\n NDRG<\/jats:styled-content>\n 4 was expressed in various neuropeptide Y positive neurons, but was only found in a minority (~10%) of neurons expressing neuronal nitric oxide synthase.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Inferences<\/jats:title>\n \n NDRG<\/jats:styled-content>\n 4 is exclusively expressed by central, peripheral and enteric neurons\/nerves, suggesting a neuronal\u2010specific role of this protein. Our findings raise the question whether\n NDRG<\/jats:styled-content>\n 4, via the\n ENS<\/jats:styled-content>\n , an understudied component of the tumor microenvironment, supports\n CRC<\/jats:styled-content>\n development and\/or progression.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/nmo.13095","type":"journal-article","created":{"date-parts":[[2017,5,19]],"date-time":"2017-05-19T06:44:06Z","timestamp":1495176246000},"source":"Crossref","is-referenced-by-count":16,"title":["NDRG<\/scp>\n 4, an early detection marker for colorectal cancer, is specifically expressed in enteric neurons"],"prefix":"10.1111","volume":"29","author":[{"given":"N.","family":"Vaes","sequence":"first","affiliation":[{"name":"Department of Pathology GROW\u2013School for Oncology and Developmental Biology Maastricht University Medical Center Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. H. F. M.","family":"Lentjes","sequence":"additional","affiliation":[{"name":"Department of Pathology GROW\u2013School for Oncology and Developmental Biology Maastricht University Medical Center Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. J.","family":"Gijbels","sequence":"additional","affiliation":[{"name":"Departments of Pathology and Molecular Genetics Cardiovascular Research Institute Maastricht (CARIM) Maastricht University Department of Medical Biochemistry Academic Medical Center Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Rademakers","sequence":"additional","affiliation":[{"name":"Department of Pathology GROW\u2013School for Oncology and Developmental Biology Maastricht University Medical Center Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K. L.","family":"Daenen","sequence":"additional","affiliation":[{"name":"Department of Pathology GROW\u2013School for Oncology and Developmental Biology Maastricht University Medical Center Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W.","family":"Boesmans","sequence":"additional","affiliation":[{"name":"Department of Pathology GROW\u2013School for Oncology and Developmental Biology Maastricht University Medical Center Maastricht The Netherlands"},{"name":"Laboratory for Enteric Neuroscience (LENS); Translational Research Center for Gastrointestinal Disorders (TARGID) Department of Clinical and Experimental Medicine University of Leuven Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K. A. D.","family":"Wouters","sequence":"additional","affiliation":[{"name":"Department of Pathology GROW\u2013School for Oncology and Developmental Biology Maastricht University Medical Center Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Geuzens","sequence":"additional","affiliation":[{"name":"Laboratory for Enteric Neuroscience (LENS); Translational Research Center for Gastrointestinal Disorders (TARGID) Department of Clinical and Experimental Medicine University of Leuven Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"X.","family":"Qu","sequence":"additional","affiliation":[{"name":"Department of Pediatric Cardiology Vanderbilt University Medical Center Nashville TN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H. P. J.","family":"Steinbusch","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neuropsychology School for Mental Health and Neuroscience (MHeNS) Maastricht University Medical Centre Maastricht The\u00a0Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B. P. F.","family":"Rutten","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neuropsychology School for Mental Health and Neuroscience (MHeNS) Maastricht University Medical Centre Maastricht The\u00a0Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. H.","family":"Baldwin","sequence":"additional","affiliation":[{"name":"Department of Pediatric Cardiology Vanderbilt University Medical Center Nashville TN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K. A.","family":"Sharkey","sequence":"additional","affiliation":[{"name":"Hotchkiss Brain Institute and Snyder Institute for Chronic Diseases Department of Physiology and Pharmacology Cumming School of Medicine University of Calgary Calgary Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. M. W.","family":"Hofstra","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics University of Rotterdam EMC Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"van Engeland","sequence":"additional","affiliation":[{"name":"Department of Pathology GROW\u2013School for Oncology and Developmental Biology Maastricht University Medical Center Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Vanden Berghe","sequence":"additional","affiliation":[{"name":"Laboratory for Enteric Neuroscience (LENS); Translational Research Center for Gastrointestinal Disorders (TARGID) Department of Clinical and Experimental Medicine University of Leuven Leuven 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