TLR4 upregulates CBS expression through NF-κB activation in a rat model of irritable bowel syndrome with chronic visceral hypersensitivity

Yuan, Bo; Wei-hong, Tang; Lu, Lijuan; Zhou, Yuan; Zhu, Hongyan; Zhou, Youlang; Zhang, Honghong; Hu, Chuang-Ying; Xu, Guang–Yin

doi:10.3748/wjg.v21.i28.8615

Cited by 27 publications

(23 citation statements)

References 41 publications

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“…In the present study, the microbial composition of MS group gut communities was associated with the enhanced functional capacity for the NF-kappa B signaling pathway. This result is consistent with previous studies indicating that neonatal MS induces VH and visceral pain in rats that is mediated by activation of TLR4 and the NF-κB signaling pathway [27,28] and further suggests that changes in the gut microbiomes caused by MS are involved in NF-κB activation in a rat model of IBS.…”

Section: Discussionsupporting

confidence: 93%

Comparison of the Gut Microbiota Disturbance in Rat Models of Irritable Bowel Syndrome Induced by Maternal Separation and Multiple Early-life Adversity

Jingzhu

Ling-peng

et al. 2020

Preprint

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Background: The aims of this study was to identify the effect of modeling procedures on bacterial communities and investigate whether different modeling procedures lead to consistent patterns of gut microbiota compositions. Methods: Two IBS rat models (MS alone and multiple-early-adversity modeling) were established and the gut microbiotas were analyzed using 16S-rRNA-based high-throughput sequencing methods. Results: Rats from both models exhibited visceral hypersensitivity and the two model groups exhibited differences in the extent of visceral sensitivity and fecal water content. The microbial community structure of the two models exhibited significant differences compared to the controls, while the two model groups also exhibited significant differences between them. Furthermore, microbial community functional predictions suggested that the two models exhibited different abundances of metabolisms and pathways. Several common and distinct characteristic differences were also observed between the two model groups. Alloprevotella were more abundant in both model groups, while Butyricicoccus, Turicibacter, Ruminococcus, and Clostridium_sensu_stricto along with the family it belongs to were less abundant relative to controls. In addition, the abundance of Clostridium_IV, Corynebacterium, Rothia, Elusimicrobium, Romboutsia, Allobaculum, Parasutterella and their related taxa were specifically associated with MS group, whereas Butyricimonas and Vampirovibrio along with its related taxa were specifically associated with MAM group. Among those, Butyricimonas, Butyricicoccus and Corynebacterium were found partially mediates early adversity exposure-induced visceral hypersensitivity. Conclusions: our results highlight the importance in evaluating gut microbiota characteristics in IBS research while also systematically considering potential modeling procedural differences. The microbial compositional/functional differences identified in this study were suggestive to further investigation of mechanism of early adversity induced IBS.

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Section: Discussionsupporting

confidence: 93%

Comparison of the Gut Microbiota Disturbance in Rat Models of Irritable Bowel Syndrome Induced by Maternal Separation and Multiple Early-life Adversity

Jingzhu

Ling-peng

et al. 2020

Preprint

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“…That periostin mediates intestinal inflammation via the activation of NF-κB pathway, which suggests that periostin may be a potential therapeutic target for inflammatory bowel disease [ 30 ] has been reported. One latest study showed that the activation of TLR4 by NCI increase CBS expression, which is mediated by the NF-κB pathway, final lead to visceral hypersensitivity [ 31 ]. In our research, we found that NF-κB p65 of model group was up-regulated, and after the inhibitor of NF-κB pathway, the expression of NF-κB p65 was down-regulated again, which revealed NF-κB pathway played a role in the mechanism of IBS.…”

Section: Discussionmentioning

confidence: 99%

Aquaporins 1, 3 and 8 expression in irritable bowel syndrome rats’ colon via NF-κB pathway

Chao

Zhang

2017

Oncotarget

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ObjectiveOur research was to detect the expression of aquaporins. NF-κB in Irritable bowel syndrome (IBS) rat models’ colon so as to find novel pathogenesisof IBS.ResultsThe expression of AQP1, AQP3, and AQP8 of IBS model group was down-regulated while NF-κB p65 was up-regulated comparing with control group (p < 0.05), and the expression of AQP1, AQP3, and AQP8 of inhibitor group was up-regulated while NF-κB p65 was down-regulated comparing with IBS model group (p < 0.05).Materials and Methods18 adult female SD big rats were divided into three groups:the rats in control group were normal rats, the rats in IBS model group and the rats of inhibitor group were injected with the inhibitor of NF-κB (PDTC). Immunohistochemical technique and western blot were performed to detect the expression of AQP1, AQP3, AQP8 and NF-κB p65. RT-PCR was performed to detect the expression of AQP1, AQP3, and AQP8.ConclusionsLiquid water metabolic abnormalities and intestine permeability alteration might be the mechanism of IBS by down-regulating AQP1, AQP3 and AQP8 via NF-κB pathway.

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“…Tamizhselvi et al [50] reported that H 2 S may up-regulate the TLR4 pathway via substance P. In accordance, our in-vitro experiment showed that the downregulation of H 2 S could markedly activate the TLR4 expression in the mouse mesangial cells. Vice versa, TLR4 was reported to upregulate CBS expression through NF-κB activation in rat [51]. Zheng et al found that compared with their wide-type counterparts, TLR4 knockout mice showed elevated expression of H 2 S-synthesizing enzyme CSE, therefore abolishing the inflammation effect of lipopolysaccharide [52].…”

Section: Discussionmentioning

confidence: 99%

High Glucose Induces Mouse Mesangial Cell Overproliferation via Inhibition of Hydrogen Sulfide Synthesis in a TLR-4-Dependent Manner

Ding¹,

Chen²,

Li³

et al. 2017

Cell Physiol Biochem

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Background/Aims: Overproliferation of mesangial cells was believed to play an important role in the progress of diabetic nephropathy, one of the primary complications of diabetes. Hydrogen sulfide (H₂S), a well-known and pungent gas with the distinctive smell of rotten eggs, was discovered to play a protective role in diabetic nephropathy. Methods: MTT assay was used to examine the viability of mesangial cells. Small interfering RNA was used to knock down the expression of TLR4 while specific inhibitor LY294002 to suppress the function of PI3K. H₂S generation rate was determined by a H₂S micro-respiration sensor. Results: Glucose of 25mM induced significant mesangial cells proliferation, which was accomplished by significantly inhibited endogenous H₂S synthesis. And exogenous H₂S treatment by NaHS markedly mitigated the overproliferation of mouse mesangial cells. Furthermore, it was found that H₂S deficiency could result in TLR4 activation. And H₂S supplementation remarkably inhibited TLR4 expression and curbed the mesangial cell overproliferation. Besides, PI3K/Akt pathway inhibition also significantly ameliorated the cell overproliferation. Conclusion: High glucose (HG) induces mouse mesangial cell overproliferation via inhibition of hydrogen sulfide synthesis in a TLR-4-dependent manner. And PI3K/Akt pathway might also play a vital part in the HG-induced mesangial cell overproliferation.

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TLR4 upregulates CBS expression through NF-κB activation in a rat model of irritable bowel syndrome with chronic visceral hypersensitivity

Abstract: Our results suggest that the activation of TLR4 by NCI upregulates CBS expression, which is mediated by the NF-κB signaling pathway, thus contributing to visceral hypersensitivity.

Cited by 27 publications

References 41 publications

Comparison of the Gut Microbiota Disturbance in Rat Models of Irritable Bowel Syndrome Induced by Maternal Separation and Multiple Early-life Adversity

Comparison of the Gut Microbiota Disturbance in Rat Models of Irritable Bowel Syndrome Induced by Maternal Separation and Multiple Early-life Adversity

Aquaporins 1, 3 and 8 expression in irritable bowel syndrome rats’ colon via NF-κB pathway

High Glucose Induces Mouse Mesangial Cell Overproliferation via Inhibition of Hydrogen Sulfide Synthesis in a TLR-4-Dependent Manner

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