Oxidative stress-induced HMGB1 translocation in myenteric neurons contributes to neuropathy in colitis

[thumbnail of biomolecules-12-01831-v2.pdf]
biomolecules-12-01831-v2.pdf - Published Version (8MB) | Preview
Available under license: Creative Commons Attribution

Stavely, Rhian, Sahakian, Lauren, Filippone, Rhiannon, Stojanovska, Vanesa, Bornstein, Joel C ORCID: 0000-0002-7518-7717, Sakkal, Samy ORCID: 0000-0003-0430-4012 and Nurgali, Kulmira ORCID: 0000-0002-2597-6929 (2022) Oxidative stress-induced HMGB1 translocation in myenteric neurons contributes to neuropathy in colitis. Biomolecules, 12 (12). ISSN 2218-273X


High-mobility group box 1 (HMGB1) is a damage-associated molecular pattern released by dying cells to stimulate the immune response. During cell death, HMGB1 is translocated from the nucleus to the cytoplasm and passively released. High levels of secreted HMGB1 are observed in the faeces of inflammatory bowel disease (IBD) patients, indicating its role in IBD pathophysiology and potential as a non-invasive IBD biomarker. HMGB1 is important in regulating neuronal damage in the central nervous system; its pathological activity is intertwined with oxidative stress and inflammation. In this study, HMGB1 expression in the enteric nervous system and its relevance to intestinal neuroinflammation is explored in organotypic cultures of the myenteric plexus exposed to oxidative stimuli and in Winnie mice with spontaneous chronic colitis. Oxidative stimuli induced cytoplasmic translocation of HMGB1 in myenteric neurons in organotypic preparations. HMGB1 translocation correlated with enteric neuronal loss and oxidative stress in the myenteric ganglia of Winnie mice. Inhibition of HMGB1 by glycyrrhizic acid ameliorated HMGB1 translocation and myenteric neuronal loss in Winnie mice. These data highlight modulation of HMGB1 signalling as a therapeutic strategy to reduce the consequences of enteric neuroinflammation in colitis, warranting the exploration of therapeutics acting on the HMGB1 pathway as an adjunct treatment with current anti-inflammatory agents.

Dimensions Badge

Altmetric Badge

Item type Article
URI https://vuir.vu.edu.au/id/eprint/46231
DOI 10.3390/biom12121831
Official URL https://www.mdpi.com/2218-273X/12/12/1831
Subjects Current > FOR (2020) Classification > 3208 Medical physiology
Current > Division/Research > Australian Institute of Musculoskeletal Science (AIMSS)
Current > Division/Research > Institute for Health and Sport
Keywords colitis, inflammation, inflammatory bowel disease, IBD, high mobility group box 1
Download/View statistics View download statistics for this item

Search Google Scholar

Repository staff login