Increased expression of CB2 receptor in the intestinal biopsies of children with inflammatory bowel disease

Strisciuglio, Caterina; Creoli, Mara; Tortora, Chiara; Martinelli, Massimo; Miele, Erasmo; Paino, Salvatore; Luongo, Livio

doi:10.1038/s41390-022-02109-5

Cited by 7 publications

(2 citation statements)

References 25 publications

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“…In an analysis of biopsies of paediatric patients, AEA levels were found to be significantly decreased in inflamed IBD mucosa [108]. A significant increase in the expression of CB 2 receptors has also been observed in the biopsies of Crohn's disease ileum and in rectum biopsies of ulcerative colitis, colocalised with T-lymphocyte infiltration [109]. Similarly, murine IBD studies demonstrated that increasing the availability of the endogenous CB 1 and CB 2 receptor agonists diminishes visceral pain [110][111][112].…”

Section: The Ecs In Ibdmentioning

confidence: 88%

Cannabis and Endometriosis: The Roles of the Gut Microbiota and the Endocannabinoid System

Farooqi,

Bhuyan,

Low

et al. 2023

JCM

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Endometriosis, a chronic condition affecting around 10–14% of women, is challenging to manage, due to its complex pathogenesis and limited treatment options. Research has suggested a potential role of the gut microbiota and the endocannabinoid system in the development and progression of endometriosis. This narrative review aims to explore the role of, and any potential interactions between, the endocannabinoid system (ECS) and the gut microbiota in endometriosis. This review found that both the ECS and microbiota influence endometriosis, with the former regulating inflammation and pain perception and the latter influencing immune responses and hormonal balance. There is evidence that a dysregulation of the endocannabinoid system and the gut microbiota influence endometriosis symptoms and progression via changes in CB1 receptor expression and increased circulating levels of endocannabinoids. Microbial imbalances in the gut, such as increases in Prevotella, have been directly correlated to increased bloating, a common endometriosis symptom, while increases in E. coli have supported the bacterial contamination hypothesis as a potential pathway for endometriosis pathogenesis. These microbial imbalances have been correlated with increases in inflammatory markers such as TNF-α and IL-6, both often raised in those with endometriosis. Protective effects of the ECS on the gut were observed by increases in endocannabinoids, including 2-AG, resulting in decreased inflammation and improved gut permeability. Given these findings, both the ECS and the gut microbiota may be targets for therapeutic interventions for endometriosis; however, clinical studies are required to determine effectiveness.

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Section: The Ecs In Ibdmentioning

confidence: 88%

Cannabis and Endometriosis: The Roles of the Gut Microbiota and the Endocannabinoid System

Farooqi,

Bhuyan,

Low

et al. 2023

JCM

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“…Although the mechanism is unclear, these findings suggest that already constitutively expressed genes were not regulated in these cells. Altogether, these limited studies suggest that CB 2 expression could be regulated by DNA methylation of its promoter and warrant future studies, especially during inflammation [ 91 , 92 , 93 ], fear memory [ 94 ], nerve injury [ 52 ], and compulsive drug abuse [ 95 ] conditions in which CB 2 expression was found to be heightened.…”

Section: Role Of Dna Methylation: Cannabinoid Receptorsmentioning

confidence: 99%

Molecular Insights into Epigenetics and Cannabinoid Receptors

Basavarajappa

Subbanna²

2022

Biomolecules

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The actions of cannabis are mediated by G protein-coupled receptors that are part of an endogenous cannabinoid system (ECS). ECS consists of the naturally occurring ligands N-arachidonylethanolamine (anandamide) and 2-arachidonoylglycerol (2-AG), their biosynthetic and degradative enzymes, and the CB1 and CB2 cannabinoid receptors. Epigenetics are heritable changes that affect gene expression without changing the DNA sequence, transducing external stimuli in stable alterations of the DNA or chromatin structure. Cannabinoid receptors are crucial candidates for exploring their functions through epigenetic approaches due to their significant roles in health and diseases. Epigenetic changes usually promote alterations in the expression of genes and proteins that can be evaluated by various transcriptomic and proteomic analyses. Despite the exponential growth of new evidence on the critical functions of cannabinoid receptors, much is still unknown regarding the contribution of various genetic and epigenetic factors that regulate cannabinoid receptor gene expression. Recent studies have identified several immediate and long-lasting epigenetic changes, such as DNA methylation, DNA-associated histone proteins, and RNA regulatory networks, in cannabinoid receptor function. Thus, they can offer solutions to many cellular, molecular, and behavioral impairments found after modulation of cannabinoid receptor activities. In this review, we discuss the significant research advances in different epigenetic factors contributing to the regulation of cannabinoid receptors and their functions under both physiological and pathological conditions. Increasing our understanding of the epigenetics of cannabinoid receptors will significantly advance our knowledge and could lead to the identification of novel therapeutic targets and innovative treatment strategies for diseases associated with altered cannabinoid receptor functions.

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Therapeutic potential of agents targeting cannabinoid type 2 receptors in organ fibrosis

Eddin,

Meeran,

Subramanya

et al. 2024

Pharmacology Res & Perspec

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The endocannabinoid system has garnered attention as a potential therapeutic target in a range of pathological disorders. Cannabinoid receptors type 2 (CB2) are a class of G protein‐coupled receptors responsible for transmitting intracellular signals triggered by both endogenous and exogenous cannabinoids, including those derived from plants (phytocannabinoids) or manufactured synthetically (synthetic cannabinoids). Recent recognition of the role of CB2 receptors in fibrosis has fueled interest in therapeutic targeting of CB2 receptors in fibrosis. Fibrosis is characterized by the alteration of the typical cellular composition within the tissue parenchyma, resulting from exposure to diverse etiological factors. The pivotal function of CB2 agonists has been widely recognized in the regulation of inflammation, fibrogenesis, and various other biological pathologies. The modulation of CB2 receptors, whether by enhancing their expression or activating their function, has the potential to provide benefits in numerous conditions, particularly by avoiding any associated adverse effects on the central nervous system. The sufficient activation of CB2 receptors resulted in the complete suppression of gene expression related to transforming growth factor β1 and its subsequent fibrogenic response. Multiple reports have also indicated the diverse functions that CB2 agonists possess in mitigating chronic inflammation and subsequent fibrosis development in various types of tissues. While currently in the preclinical stage, the advancement of CB2 compounds has garnered significant attention within the realm of drug discovery. This review presents a comprehensive synthesis of various independent experimental studies elucidating the pivotal role of identified natural and synthetic CB2 agonists in the pathophysiology of organ fibrosis, specifically in the cardiac, hepatic, and renal systems.

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Increased expression of CB2 receptor in the intestinal biopsies of children with inflammatory bowel disease

Cited by 7 publications

References 25 publications

Cannabis and Endometriosis: The Roles of the Gut Microbiota and the Endocannabinoid System

Cannabis and Endometriosis: The Roles of the Gut Microbiota and the Endocannabinoid System

Molecular Insights into Epigenetics and Cannabinoid Receptors

Therapeutic potential of agents targeting cannabinoid type 2 receptors in organ fibrosis

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