Effect of TrkB-PLC/IP3 pathway on intestinal inflammatory factors and enterocyte apoptosis in mice with colitis

Xu, Guangmeng; Sun, Yuxin; He, Hangyong; Xue, Qiuli; Liu, Huan; Dong, Ling

doi:10.1093/abbs/gmaa044

Cited by 12 publications

(6 citation statements)

References 30 publications

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“…In the UC mouse model, inhibition of the TrkB-PLC/IP3 pathway resulted in a blocked enterocyte cycle and a greater rate of apoptosis in a mice colitis model [ 62 ]. Moreover, the study group experienced a more severe course of the disease (as assessed by disease activity, colon mucosa, and tissue damage indexes) and altered cytokine profile due to elevated expression of IL-4,8 and down-regulated IL-10, which created a pro-inflammatory milieu [ 62 ]. In one study, CD patients had higher serum BDNF than healthy controls [ 61 ].…”

Section: Bdnf In Immune-related Diseasesmentioning

confidence: 99%

The Role of Brain-Derived Neurotrophic Factor in Immune-Related Diseases: A Narrative Review

Sochal

Ditmer

Gabryelska

et al. 2022

JCM

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Brain-derived neurotrophic factor (BDNF) is a neurotrophin regulating synaptic plasticity, neuronal excitability, and nociception. It seems to be one of the key molecules in interactions between the central nervous system and immune-related diseases, i.e., diseases with an inflammatory background of unknown etiology, such as inflammatory bowel diseases or rheumatoid arthritis. Studies show that BDNF levels might change in the tissues and serum of patients during the course of these conditions, e.g., affecting cell survival and modulating pain severity and signaling pathways involving different neurotransmitters. Immune-related conditions often feature psychiatric comorbidities, such as sleep disorders (e.g., insomnia) and symptoms of depression/anxiety; BDNF may be related as well to them as it seems to exert an influence on sleep structure; studies also show that patients with psychiatric disorders have decreased BDNF levels, which increase after treatment. BDNF also has a vital role in nociception, particularly in chronic pain, hyperalgesia, and allodynia, participating in the formation of central hypersensitization. In this review, we summarize the current knowledge on BDNF’s function in immune-related diseases, sleep, and pain. We also discuss how BDNF is affected by treatment and what consequences these changes might have beyond the nervous system.

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Section: Bdnf In Immune-related Diseasesmentioning

confidence: 99%

The Role of Brain-Derived Neurotrophic Factor in Immune-Related Diseases: A Narrative Review

Sochal

Ditmer

Gabryelska

et al. 2022

JCM

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“…Jejunum tissues of rats were taken for routine fixation and paraffin embedding, followed by sectioning and H&E staining and then histologically estimated under light microscope. Tissue damage index (TDI) scores were evaluated according to standards previously reported ( Xu et al, 2020 ). The scoring indexes were set up at 0–3 points according to the degree of lesions, including epithelial injury, ulcer depth, lymphocyte infiltration, edema and infiltration of inflammatory cells (such as neutrophils and eosinophilic cells).…”

Section: Methodsmentioning

confidence: 99%

Sanguinarine protects against indomethacin-induced small intestine injury in rats by regulating the Nrf2/NF-κB pathways

et al. 2022

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In recent years, small intestine as a key target in the treatment of Inflammatory bowel disease caused by NSAIDs has become a hot topic. Sanguinarine (SA) is one of the main alkaloids in the Macleaya cordata extracts with strong pharmacological activity of anti-tumor, anti-inflammation and anti-oxidant. SA is reported to inhibit acetic acid-induced colitis, but it is unknown whether SA can relieve NSAIDs-induced small intestinal inflammation. Herein, we report that SA effectively reversed the inflammatory lesions induced by indomethacin (Indo) in rat small intestine and IEC-6 cells in culture. Our results showed that SA significantly relieved the symptoms and reversed the inflammatory lesions of Indo as shown in alleviation of inflammation and improvement of colon macroscopic damage index (CMDI) and tissue damage index (TDI) scores. SA decreased the levels of TNF-α, IL-6, IL-1β, MDA and LDH in small intestinal tissues and IEC-6 cells, but increased SOD activity and ZO-1 expression. Mechanistically, SA dose-dependently promoted the expression of Nrf2 and HO-1 by decreasing Keap-1 level, but inhibited p65 phosphorylation and nuclear translocation in Indo-treated rat small intestine and IEC-6 cells. Furthermore, in SA treated cells, the colocalization between p-p65 and CBP in the nucleus was decreased, while the colocalization between Nrf2 and CBP was increased, leading to the movement of gene expression in the nucleus to the direction of anti-inflammation and anti-oxidation. Nrf2 silencing blocked the effects of SA. Together our results suggest that SA can significantly prevent intestinal inflammatory lesions induced by Indo in rats and IEC-6 cells through regulation of the Nrf2 pathway and NF-κBp65 pathway.

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“…Impairment of the enteric glia, caused by BDNF deficiency, might lead to malfunctioning of the intestinal barrier, which may contribute to IBD pathogenesis [ 18 , 19 ]. Blockade of the TrkB-PLC/IP3 pathway in experimental colitis in mice had detrimental consequences [ 20 ]. It increased the enterocyte apoptosis rate and shifted the cytokine profile towards more pro-inflammatory, which resulted in a more severe disease course, confirmed by biopsy findings [ 20 ].…”

Section: Introductionmentioning

confidence: 99%

“…Blockade of the TrkB-PLC/IP3 pathway in experimental colitis in mice had detrimental consequences [ 20 ]. It increased the enterocyte apoptosis rate and shifted the cytokine profile towards more pro-inflammatory, which resulted in a more severe disease course, confirmed by biopsy findings [ 20 ].…”

Section: Introductionmentioning

confidence: 99%

Relation between Selected Sleep Parameters, Depression, Anti-Tumor Necrosis Factor Therapy, and the Brain-Derived Neurotrophic Factor Pathway in Inflammatory Bowel Disease

et al. 2023

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Inflammatory bowel disease (IBD) patients often have sleep and mood disorders. Brain-derived neurotrophic factor (BDNF) and proBDNF were shown to modulate interactions between the central nervous system and the gastrointestinal tract, possibly contributing to psychological issues. Anti-tumor necrosis factor (TNF) therapy in IBD can alter BDNF expression and further affect the brain–gut axis. Eighty IBD patients and 44 healthy controls (HCs) were enrolled and divided into subsets based on disease activity and condition (ulcerative colitis (UC)/Crohn’s disease (CD)). Questionnaires evaluating sleep parameters and depression as well as venous blood were collected. The IBD group had a lower expression of BDNF mRNA, but higher proBDNF and BDNF protein concentration than HCs. The UC group had a higher BDNF protein concentration than the CD. BDNF protein was positively correlated to sleep efficiency in the IBD group. Depression severity was associated positively with BDNF mRNA and negatively with BDNF protein in the remission group. Anti-TNF therapy enhanced BDNF mRNA expression. The BDNF pathway might be disturbed in IBD, linking it to sleep disorders and depression. Systemic inflammation could be the main cause of this disruption. BDNF mRNA is a more reliable parameter than protein due to numerous post-translational modifications.

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Effect of TrkB-PLC/IP3 pathway on intestinal inflammatory factors and enterocyte apoptosis in mice with colitis

Cited by 12 publications

References 30 publications

The Role of Brain-Derived Neurotrophic Factor in Immune-Related Diseases: A Narrative Review

The Role of Brain-Derived Neurotrophic Factor in Immune-Related Diseases: A Narrative Review

Sanguinarine protects against indomethacin-induced small intestine injury in rats by regulating the Nrf2/NF-κB pathways

Relation between Selected Sleep Parameters, Depression, Anti-Tumor Necrosis Factor Therapy, and the Brain-Derived Neurotrophic Factor Pathway in Inflammatory Bowel Disease

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