{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:57:02Z","timestamp":1792803422127,"version":"4.5.0"},"reference-count":73,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2024,8,12]],"date-time":"2024-08-12T00:00:00Z","timestamp":1723420800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Medical Faculty Mannheim, University of Heidelberg","id":[{"id":"https:\/\/ror.org\/038t36y30","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Hirschsprung\u2019s disease (HSCR, incidence 1\/5000 live births) is caused by the failure of neural crest-derived precursors to migrate, survive, proliferate, or differentiate during the embryonic development of the Enteric Nervous System (ENS), which could be disrupted by many factors, including inflammatory processes. The NF-\u03baB family controls several biological processes, including inflammation, neurogenesis, and cell migration. With the aim of studying the potential role of NF-\u03baB in HSCR, we have analyzed the expression of the NF-\u03baB main subunits and other NF-\u03baB-related genes by RT-qPCR in HSCR tissue samples (sub-divided into ganglionic and aganglionic segments). We found decreased gene expression of the NF-\u03baB main subunit RELA but also of NFKBIA, TNFA, TFGBR2, and ERBB3 in the pathologic distal aganglionic segments compared to the proximal ganglionic segments. Moreover, we could also confirm the lower protein expression of RelA\/p65 in the aganglionic distal segments by immunofluorescence staining. Further, we show that the expression of RelA\/p65 protein in the proximal segments concurs with lymphocyte infiltration in the bowel tissue, indicating a pro-inflammatory activation of p65 in the proximal ganglionic HSCR tissue in the patients analyzed. All in all, our findings suggest that the modulation of NF-\u03baB signaling in the neuro-enteric system does obviously contribute to the pathological effects of HSCR.<\/jats:p>","DOI":"10.3390\/biom14080992","type":"journal-article","created":{"date-parts":[[2024,8,14]],"date-time":"2024-08-14T06:23:05Z","timestamp":1723616585000},"page":"992","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Role of Inflammation and the NF-\u03baB Signaling Pathway in Hirschsprung\u2019s Disease"],"prefix":"10.3390","volume":"14","author":[{"given":"Enas Zoheer","family":"Elkrewi","sequence":"first","affiliation":[{"name":"Department of Pediatric Surgery, Medical Faculty of Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1\u20133, 68167 Mannheim, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7515-5662","authenticated-orcid":false,"given":"Ahmad A.","family":"Al Abdulqader","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, Medical Faculty of Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1\u20133, 68167 Mannheim, Germany"},{"name":"Department of Surgery, College of Medicine, King Faisal University, Al Hofuf 31982, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rasul","family":"Khasanov","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, Medical Faculty of Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1\u20133, 68167 Mannheim, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silke","family":"Maas-Omlor","sequence":"additional","affiliation":[{"name":"Working Group Enteric Nervous Systems (AGENS), University of Applied Sciences Kaiserslautern, Amerikastrasse 1,66482 Zweibr\u00fccken, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4972-9866","authenticated-orcid":false,"given":"Michael","family":"Boettcher","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, Medical Faculty of Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1\u20133, 68167 Mannheim, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8574-1403","authenticated-orcid":false,"given":"Lucas M.","family":"Wessel","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, Medical Faculty of Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1\u20133, 68167 Mannheim, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl-Herbert","family":"Sch\u00e4fer","sequence":"additional","affiliation":[{"name":"Working Group Enteric Nervous Systems (AGENS), University of Applied Sciences Kaiserslautern, Amerikastrasse 1,66482 Zweibr\u00fccken, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6578-6495","authenticated-orcid":false,"given":"Mar\u00eda \u00c1ngeles","family":"Tapia-Laliena","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, Medical Faculty of Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1\u20133, 68167 Mannheim, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1038\/nrgastro.2017.149","article-title":"Hirschsprung Disease\u2014Integrating Basic Science and Clinical Medicine to Improve Outcomes","volume":"15","author":"Heuckeroth","year":"2018","journal-title":"Nat. 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