Involvement of Corticotropin-Releasing Factor and Receptors in Immune Cells in Irritable Bowel Syndrome

Chatoo, Mahanand; Yi, Li; Ma, Zhiqiang; Coote, John H.; Du, Ji-Zeng

doi:10.3389/fendo.2018.00021

Cited by 42 publications

(37 citation statements)

References 73 publications

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“…The CRF system also influences some functions within the gastrointestinal system, including gut motility and permeability [67]. Interestingly, animal studies showed that increased CRF might be associated with alteration in the intestinal microbial community (i.e., reduction in Lactobacillus), as well, an opposite relation has been found between alteration of the CRF signaling (i.e., CRF-mediated activation of the HPA axis) and changes in the gut microbiota [68].…”

Section: Gut-brain Axismentioning

confidence: 99%

Diet and Mental Health: Review of the Recent Updates on Molecular Mechanisms

et al. 2020

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Over the last decades, there has been a substantial increase in the prevalence of mental health disorders, including an increased prevalence of depression, anxiety, cognitive, and sleep disorders. Diet and its bioactive components have been recognized among the modifiable risk factors, possibly influencing their pathogenesis. This review aimed to summarize molecular mechanisms underlying the putative beneficial effects toward brain health of different dietary factors, such as micro- and macronutrient intake and habits, such as feeding time and circadian rhythm. The role of hormonal homeostasis in the context of glucose metabolism and adiponectin regulation and its impact on systemic and neuro-inflammation has also been considered and deepened. In addition, the effect of individual bioactive molecules exerting antioxidant activities and acting as anti-inflammatory agents, such as omega-3 fatty acids and polyphenols, considered beneficial for the central nervous system via modulation of adult neurogenesis, synaptic and neuronal plasticity, and microglia activation has been summarized. An overview of the regulation of the gut–brain axis and its effect on the modulation of systemic inflammation and oxidative stress has been provided. Finally, the impact of bioactive molecules on inflammation and oxidative stress and its association with brain health has been summarized.

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Section: Gut-brain Axismentioning

confidence: 99%

Diet and Mental Health: Review of the Recent Updates on Molecular Mechanisms

et al. 2020

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“…These neuroendocrine peptides are best known for their involvement in regulating the physiological and behavioural responses to stress, through the cognate G-protein-coupled receptors (GPCRs), CRH receptor 1 (CRHR1) and CRH receptor 2 (CRHR2) (Chen et al 1993, Lovenberg et al 1995, Weninger et al 1999, Bakshi et al 2002, as part of the hypothalamic-pituitary-adrenal (HPA) axis. More recent evidence suggests additional, diverse, extra-hypothalamic roles for these peptides in peripheral organs (Paschos et al 2013, Chatoo et al 2018, Chatzaki et al 2019. Thus, CRH expression has been reported in the adrenal gland and the gastrointestinal tract (Suda et al 1984); UCN1 is expressed in heart, skin and adipose tissue (Kimura et al 2002, Seres et al 2004, Wierzbicka et al 2017; and UCN2 and UCN3 have been detected in peripheral blood cells, skeletal muscle, pancreas and gestational tissues such as foetal membranes and placental villi (Petraglia et al 2010).…”

Section: Introductionmentioning

confidence: 99%

UCN2: a new candidate influencing pancreatic β-cell adaptations in pregnancy

Simpson

Smith

Jones

et al. 2020

Journal of Endocrinology

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The corticotropin-releasing hormone (CRH) family of peptides, including urocortin (UCN) 1, 2 and 3, are established hypothalamic neuroendocrine peptides, regulating the physiological and behaviour responses to stress indirectly, via the hypothalamic-pituitary-adrenal (HPA) axis. More recently, these peptides have been implicated in diverse roles in peripheral organs through direct signalling, including in placental and pancreatic islet physiology. CRH has been shown to stimulate insulin release through activation of its cognate receptors, CRH receptor 1 (CRHR1) and 2. However, the physiological significance of this is unknown. We have previously reported that during mouse pregnancy, expression of CRH peptides increase in mouse placenta suggesting that these peptides may play a role in various biological functions associated with pregnancy, particularly the pancreatic islet adaptations that occur in the pregnant state to compensate for the physiological increase in maternal insulin resistance. In the current study, we show that mouse pregnancy is associated with increased circulating levels of UCN2 and that when we pharmacologically block endogenous CRHR signalling in pregnant mice, impairment of glucose tolerance is observed. This effect on glucose tolerance was comparable to that displayed with specific CRHR2 blockade and not with specific CRHR1 blockade. No effects on insulin sensitivity or the proliferative capacity of β-cells were detected. Thus, CRHR2 signalling appears to be involved in β-cell adaptive responses to pregnancy in the mouse, with endogenous placental UCN2 being the likely signal mediating this.

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“…The CRF system also modulates visceral hypersensitivity [26] and gut motility in animal models of stress [27]. It is also implicated in the modulation of gut motility and mood behavior in IBS patients [28]. We previously documented increased levels of CRFRs in duodenal biopsies of patients with Crohn’s disease [15], but the status of CRFRs in IBS patients is unknown.…”

Section: Introductionmentioning

confidence: 99%

Plasma Corticotropin-Releasing Factor Receptors and B7-2+ Extracellular Vesicles in Blood Correlate with Irritable Bowel Syndrome Disease Severity

Hagiwara

Hasdemir

Heyman

et al. 2019

Cells

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Extracellular vesicles (EVs) are composed of bilayer membranes that are released by different cell types and are present in bodily fluids, such as blood, urine, and bile. EVs are thought to play a key role in intracellular communication. Based on their size and density, EVs are classified into small, medium, or large EVs. Cargo composition in EVs reflects physiological changes in health and disease. Patients with irritable bowel syndrome (IBS) exhibit visceral hypersensitivity and mood disorders. Stressful episodes often precede disease symptoms in IBS patients. Stress-induced symptoms include, but are not limited to, abdominal pain and mood swings. Perceived stress responses are mediated by two known G protein-coupled receptors (GPCRs), corticotropin-releasing factor receptor 1 and 2 (CRFRs). CRFRs belong to the Class B secretin receptor family of GPCRs. Here, we show that CRFRs were present in human and murine plasma, and in EVs purified from mouse serum. CRFRs were present in plasma from IBS patients and healthy controls. EVs secreted from immune cells influence both adaptive and innate immune responses via exchange of EVs between different immune cell types. B7-2 (CD86), a plasma membrane antigen-presenting protein, is present on EVs secreted from dendritic, B-, and mast cells, whereas CD9 is present on EVs secreted from dendritic and intestinal epithelial cells. We found that plasma CRFR levels positively correlated with B7-2+ EVs (R = 0.8597, p < 0.0001), but no association was seen with CD9+ EVs. Plasma CRFRs expression negatively correlated with IBS severity scores. Our data suggests that plasma EVs from immune cells carry CRFRs as cargos and influence cell-cell communication in health and disease.

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Involvement of Corticotropin-Releasing Factor and Receptors in Immune Cells in Irritable Bowel Syndrome

Cited by 42 publications

References 73 publications

Diet and Mental Health: Review of the Recent Updates on Molecular Mechanisms

Diet and Mental Health: Review of the Recent Updates on Molecular Mechanisms

UCN2: a new candidate influencing pancreatic β-cell adaptations in pregnancy

Plasma Corticotropin-Releasing Factor Receptors and B7-2+ Extracellular Vesicles in Blood Correlate with Irritable Bowel Syndrome Disease Severity

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