The Role of E3 Ubiquitin Ligases and Deubiquitinases in Inflammatory Bowel Disease: Friend or Foe?

Inflammatory bowel disease (IBD), which include Crohn’s disease (CD) and ulcerative colitis (UC), exhibits a complex multifactorial pathogenesis involving genetic susceptibility, imbalance of gut microbiota, mucosal immune disorder and environmental factors. Recent studies reported associations between ubiquitination and deubiquitination and the occurrence and development of inflammatory bowel disease. Ubiquitination modification, one of the most important types of post-translational modifications, is a multi-step enzymatic process involved in the regulation of various physiological processes of cells, including cell cycle progression, cell differentiation, apoptosis, and innate and adaptive immune responses. Alterations in ubiquitination and deubiquitination can lead to various diseases, including IBD. Here, we review the role of E3 ubiquitin ligases and deubiquitinases (DUBs) and their mediated ubiquitination and deubiquitination modifications in the pathogenesis of IBD. We highlight the importance of this type of posttranslational modification in the development of inflammation, and provide guidance for the future development of targeted therapeutics in IBD.

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Role of RING-Type E3 Ubiquitin Ligases in Inflammatory Signalling and Inflammatory Bowel Disease

Mediators of Inflammation ◽

10.1155/2020/5310180 ◽

2020 ◽

Vol 2020 ◽

pp. 1-10

Author(s):

Liguo Zhu ◽

Ying Li ◽

Longyuan Zhou ◽

Guang Yang ◽

Ying Wang ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Protein Modification ◽

Ubiquitin Ligases ◽

E3 Ubiquitin Ligases ◽

Ring Type ◽

Ubiquitin Ligase E3 ◽

Inflammatory Bowel ◽

Inflammatory Signalling ◽

Functional Mechanisms

Ubiquitination is a three-step enzymatic cascade for posttranslational protein modification. It includes the ubiquitin-activating enzyme (E1), ubiquitin-conjugating enzyme (E2), and ubiquitin ligase (E3). RING-type E3 ubiquitin ligases catalyse the posttranslational proteolytic and nonproteolytic functions in various physiological and pathological processes, such as inflammation-associated signal transduction. Resulting from the diversity of substrates and functional mechanisms, RING-type ligases regulate microbe recognition and inflammation by being involved in multiple inflammatory signalling pathways. These processes also occur in autoimmune diseases, especially inflammatory bowel disease (IBD). To understand the importance of RING-type ligases in inflammation, we have discussed their functional mechanisms in multiple inflammation-associated pathways and correlation between RING-type ligases and IBD. Owing to the limited data on the biology of RING-type ligases, there is an urgent need to analyse their potential as biomarkers and therapeutic targets in IBD in the future.

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The role of osteopontin (OPN/SSP1) gene variants in inflammatory bowel disease

Zeitschrift für Gastroenterologie ◽

10.1055/s-0029-1241334 ◽

2009 ◽

Vol 47 (09) ◽

Author(s):

J Glas ◽

J Seiderer ◽

HP Török ◽

B Göke ◽

T Ochsenkühn ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Gene Variants ◽

Inflammatory Bowel

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Nutrition in inflammatory bowel disease

Orvosi Hetilap ◽

10.1556/oh.2009.28599 ◽

2009 ◽

Vol 150 (18) ◽

pp. 839-845 ◽

Cited By ~ 2

Author(s):

János Banai

Keyword(s):

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Fast Food ◽

Optimal Growth ◽

Developed Countries ◽

Aetiological Factor ◽

Artificial Nutrition ◽

Food Preservatives ◽

Inflammatory Bowel

Aetiology of inflammatory bowel disease (IBD) is complex and probably multifactorial. Nutrition has been proposed to be an important aetiological factor for development of IBD. Several components of the diet (such as sugar, fat, fibre, fruit and vegetable, protein, fast food, preservatives etc.) were examined as possible causative agents for IBD. According to some researchers infant feeding (breast feeding) may also contribute to the development of IBD. Though the importance of environmental factors is evidenced by the increasing incidence in developed countries and in migrant population in recent decades, the aetiology of IBD remained unclear. There are many theories, but as yet no dietary approaches have been proved to reduce the risk of developing IBD. The role of nutrition in the management of IBD is better understood. The prevention and correction of malnutrition, the provision of macro- and micronutrients and vitamins and the promotion of optimal growth and development of children are key points of nutritional therapy. In active disease, the effective support of energy and nutrients is a very important part of the therapy. Natural and artificial nutrition or the combination of two can be choosen for supporting therapy of IBD. The author summarises the aetiological and therapeutic role of nutrition in IBD.

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Role of Rifaximin in Inflammatory Bowel Disease Treatment

Mini-Reviews in Medicinal Chemistry ◽

10.2174/1389557515666150722104230 ◽

2015 ◽

Vol 16 (3) ◽

pp. 225-229 ◽

Cited By ~ 2

Author(s):

Maria Lia Scribano

Keyword(s):

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Disease Treatment ◽

Inflammatory Bowel

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Tu1789 – Treatment Response to Ustekinumab and Vedolizumab in Inflammatory Bowel Disease: the Predictive Role of Gut Microbiota

Gastroenterology ◽

10.1016/s0016-5085(19)39775-6 ◽

2019 ◽

Vol 156 (6) ◽

pp. S-1124

Author(s):

Clara Caenepeel ◽

Sara Vieira-Silva ◽

Jorge F. Vázquez-Castellanos ◽

Bram Verstockt ◽

Marc Ferrante ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Gut Microbiota ◽

Treatment Response ◽

Bowel Disease ◽

Predictive Role ◽

Inflammatory Bowel

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The role of heme oxygenase and carbon monoxide in inflammatory bowel disease

Redox Report ◽

10.1179/174329210x12650506623889 ◽

2010 ◽

Vol 15 (5) ◽

pp. 193-201 ◽

Cited By ~ 20

Author(s):

Tomohisa Takagi ◽

Yuji Naito ◽

Kazuhiko Uchiyama ◽

Toshikazu Yoshikawa

Keyword(s):

Inflammatory Bowel Disease ◽

Carbon Monoxide ◽

Heme Oxygenase ◽

Bowel Disease ◽

Inflammatory Bowel

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Ethnic Differences in the Smoking-Related Risk of Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjab047 ◽

2021 ◽

Author(s):

Daniele Piovani ◽

Claudia Pansieri ◽

Soumya R R Kotha ◽

Amanda C Piazza ◽

Celia-Louise Comberg ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Latin American ◽

Bowel Disease ◽

Meta Analysis ◽

Study Data ◽

Future Research ◽

Related Risk ◽

Increased Risk ◽

Inflammatory Bowel

Abstract Background and aims The association between smoking and inflammatory bowel disease (IBD) relies on old meta-analyses including exclusively non-Jewish White populations. Uncertainty persists regarding the role of smoking in other ethnicities. Methods We systematically searched Medline/PubMed, Embase and Scopus for studies examining tobacco smoking and the risk of developing IBD, i.e., Crohn’s disease (CD) or ulcerative colitis (UC). Two authors independently extracted study data and assessed each study’s risk-of-bias. We examined heterogeneity and small-study effect, and calculated summary estimates using random-effects models. Stratified analyses and meta-regression were employed to study the association between study-level characteristics and effect estimates. The strength of epidemiological evidence was assessed through prespecified criteria. Results We synthesized 57 studies examining the smoking-related risk of developing CD and UC. Non-Jewish White smokers were at increased risk of CD (29 studies; RR: 1.95, 95% CI: 1.69‒2.24; moderate evidence). No association was observed in Asian, Jewish and Latin-American populations (11 studies; RR: 0.97; 95% CI: 0.83–1.13), with no evidence of heterogeneity across these ethnicities. Smokers were at reduced risk of UC (51 studies; RR: 0.55, 95% CI: 0.48–0.64; weak evidence) irrespectively of ethnicity; however, cohort studies, large studies and those recently published showed attenuated associations. Conclusions This meta-analysis did not identify any increased risk of CD in smokers in ethnicities other than non-Jewish Whites, and confirmed the protective effect of smoking on UC occurrence. Future research should characterize the genetic background of CD patients across different ethnicities to improve our understanding on the role of smoking in CD pathogenesis.

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