Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Role of Inflammation and the NF-κB Signaling Pathway in Hirschsprung Disease

Version 1 : Received: 20 June 2024 / Approved: 20 June 2024 / Online: 21 June 2024 (13:13:49 CEST)

How to cite: Elkrewi, E. Z.; Al Abdulqader, A. A.; Khasanov, R. R.; Maas-Omlor, S.; Wessel, L. M.; Boettcher, M.; Schäfer, K. H.; Tapia-Laliena, M. Á. Role of Inflammation and the NF-κB Signaling Pathway in Hirschsprung Disease. Preprints 2024, 2024061531. https://doi.org/10.20944/preprints202406.1531.v1 Elkrewi, E. Z.; Al Abdulqader, A. A.; Khasanov, R. R.; Maas-Omlor, S.; Wessel, L. M.; Boettcher, M.; Schäfer, K. H.; Tapia-Laliena, M. Á. Role of Inflammation and the NF-κB Signaling Pathway in Hirschsprung Disease. Preprints 2024, 2024061531. https://doi.org/10.20944/preprints202406.1531.v1

Abstract

Hirschsprung disease (HSCR, incidence 1/5000 live births) is caused by 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, in-cluding inflammatory processes. The NF-κB family controls several biological processes includ-ing inflammation, neurogenesis and cell migration. With the aim of studying the potential role of NF-κB in HSCR, we have analyzed the expression of the NF-κB main subunits and other NF-κB-related genes by RT-qPCR in HSCR tissue samples (sub-divided in ganglionic and agan-glionic segments). We found a decreased gene expression of the NF-κB main subunit RelA/p65, but also of IkBα, TNF-α, TFGBR2 and ERBB3 in the pathologic distal aganglionic segments com-pared 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. Fur-ther, we show that the expression of RelA/p65 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. In all, our findings suggest that the modulation of NF-κB signaling in the neuro-enteric system does obviously contribute to the pathological ef-fects in HSCR.

Keywords

Hirschsprung disease (HSCR); Enteric Nervous System (ENS); NF-κB pathway; inflammation; neuronal migration

Subject

Biology and Life Sciences, Neuroscience and Neurology

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