Functional screen of Inflammatory bowel disease genes reveals key epithelial functions

Ntunzwenimana, Jessy Carol; Boucher, Gabrielle; Paquette, Jean; Gosselin, Hugues; Alikashani, Azadeh; Morin, Nicolas; Beauchamp, Claudine; Thauvette, Louise; Rivard, Marie-Ève; Dupuis, Frédérique; Deschênes, Sylvain; Foisy, Sylvain; Latour, Frédéric; Lavallée, Geneviève; Daly, Mark J.; Xavier, Ramnik J.; Charron, Guy; Goyette, Philippe; Rioux, John D.

doi:10.1101/2021.10.15.464566

Cited by 10 publications

(9 citation statements)

References 90 publications

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“…Our study additionally suggested that the TLR4/MAPK/ NF-κB signaling pathway was involved in the regulation of CJ in UC. Existing evidence identifies NFKB1 as a causal gene in the pathogenesis of inflammatory bowel diseases [31]. Inhibition of the TLR4/NF-κB pathway is associated with an alleviative effect on DSS-elicited colitis [32].…”

Section: Discussionmentioning

confidence: 99%

Cayratia japonica Prevents Ulcerative Colitis by Promoting M2 Macrophage Polarization through Blocking the TLR4/MAPK/NF-κB Pathway

Sun

Zhao

Ding

et al. 2022

Mediators of Inflammation

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Background and Aims. Several components of Cayratia japonica (CJ) such as rutin and quercetin have shown anti-inflammatory effect, yet its function in ulcerative colitis (UC) remains to be clarified. This study focuses on the modulatory effect of CJ on UC as well as molecular mechanism by which CJ regulates macrophage polarization in UC. Methods. The targets related to CJ components and UC were, respectively, obtained through in silico analysis, and their intersection targets were selected for pathway enrichment analysis. RAW264.7 cells were stimulated with lipopolysaccharide (LPS) to induce M1 macrophages. Expression of the macrophage polarization M1 marker CD11b and M2 marker CD206 was measured to determine the phenotype of macrophages. The mouse model was treated with dextran sodium sulfate (DSS) to induce UC to observe the effects of CJ on UC in vivo. Results. The in silico analysis suggested the crucial significance of TLR4 and its downstream MAPK/NF-κB pathways in the modulatory effect of CJ on UC. Furthermore, experimental data revealed that CJ could promote M2 macrophage polarization but alleviate immune inflammation and reduce colon damage in DSS-evoked UC model. Additionally, CJ can inhibit the expression of TLR4/MAPK/NF-κB signaling pathway to enhance the M2-like polarization. Conclusion. Hence, CJ may exert anti-inflammatory effects and an inhibitory role in UC by inhibiting the TLR4/MAPK/NF-κB pathway and subsequent M1-like macrophage polarization.

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Section: Discussionmentioning

confidence: 99%

Cayratia japonica Prevents Ulcerative Colitis by Promoting M2 Macrophage Polarization through Blocking the TLR4/MAPK/NF-κB Pathway

Sun

Zhao

Ding

et al. 2022

Mediators of Inflammation

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“…Several pre-clinical experiments, including the data presented in this contribution, have demonstrated a potential for NCT to exert a HNF4α-mediated benefit on intestinal function. Additionally, HNF4α has a well-documented effect on epithelial cell transcription activity and the related transcriptome (Ntunzwenimana et al, 2021). In patients with ulcerative colitis, HNF4α is significantly downregulated compared to controls, suggesting a role in the disease state (Vancamelbeke et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

Impact of selected novel plant bioactives on improvement of impaired gut barrier function using human primary cell intestinal epithelium

Bolster¹,

Chae²,

Klinken³

et al. 2022

Journal of Food Bioactives

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Gut barrier function is compromised in the obese state. The N-trans caffeoyltyramine (NCT) and N-trans feruloyltyramine (NFT), two naturally occurring bioactive compounds in hemp hulls, identified using in silico approaches, have the potential to improve gut barrier function and their effects were studied here in vitro. Proliferative human transverse colon epithelial cells were plated and co-cultured with tumor necrosis factor (TNF) along with NCT, NFT or NCT/NFT (2.2 ratio) post-differentiation, over a 48-hour period to induce inflammation and to observe the effects of NCT and NFT. A decrease in transepithelial electrical resistance (TEER) and increase in the intestinal permeability were observed with increased addition of TNF. Co-administration of NCT and NFT demonstrated a dose-dependent and statistically significant reversal of impaired TEER and intestinal permeability. NCT and NFT demonstrated a physiologically relevant reversal of impaired gut barrier function in the setting of inflammation via significant improvement in TEER and percent permeability.

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“…High-density genotyping, targeted sequencing studies, whole-exome sequencing and whole genome sequencing studies have identified the approximately 20 causal genes. Importantly, these studies have revealed key biological functions in the pathogenesis of IBD, including microbial recognition, autophagy, cytokine signaling, and intestinal epithelial barrier function [28].…”

Section: Inflammatory Bowel Disease (Ibd) Is An Intractable Bowel Dis...mentioning

confidence: 99%

Mitotic spindle positioning protein (MISP) deficiency exacerbates dextran sulfate sodium (DSS)-induced colitis in mice

Hiura

Maruyama

Watanabe

et al. 2023

The Journal of Veterinary Medical Science

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Inflammatory bowel disease (IBD) is classified into two types: Crohn's disease and ulcerative colitis. In IBD, the imbalance between the pro-inflammatory and anti-inflammatory cytokines prevents recovery from the inflammatory state, resulting in chronic inflammation in the colon.The mitotic spindle positioning protein (MISP) is localized to the apical membrane in the colon.In this study, we observed increased expression of MISP in the intestinal epithelial cells in dextran sulfate sodium (DSS)-induced colitis in mice. MISP-deficient mice receiving DSS showed significant exacerbation of colitis (e.g., weight loss, loss of the crypts). The intestinal epithelial cells of the MISP-deficient mice showed a trend towards decreased cell proliferation after DSS treatment. Reverse transcription followed by quantitative polymerase chain reaction revealed that the expression levels of Tgfb1, an anti-inflammatory cytokine, were significantly reduced in the colon of MISP-deficient mice compared with the wild-type mice regardless of DSS treatment.These findings indicate that MISP may play a role in the recovery of the colon after inflammation through its anti-inflammatory and proliferative activities, suggesting that MISP may be a new therapeutic target for IBD.

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Functional screen of Inflammatory bowel disease genes reveals key epithelial functions

Cited by 10 publications

References 90 publications

Cayratia japonica Prevents Ulcerative Colitis by Promoting M2 Macrophage Polarization through Blocking the TLR4/MAPK/NF-κB Pathway

Cayratia japonica Prevents Ulcerative Colitis by Promoting M2 Macrophage Polarization through Blocking the TLR4/MAPK/NF-κB Pathway

Impact of selected novel plant bioactives on improvement of impaired gut barrier function using human primary cell intestinal epithelium

Mitotic spindle positioning protein (MISP) deficiency exacerbates dextran sulfate sodium (DSS)-induced colitis in mice

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