Alcohol promotes macrophage M2b polarization in colitis by modulating the TRPV1-MAPK/NF-kB pathways
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ABSTRACT:
PROVIDER: PRJNA996605 | ENA |
REPOSITORIES: ENA
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Project description:Macrophages are key immune cells in inflammatory bowel disease (IBD) that can exhibit different phenotypes and promote inflammation. Alcohol consumption is associated with increased risk and severity of IBD. We performed in vitro and in vivo experiments with dextran sodium sulfate-induced mice colitis model, peritoneal macrophages and RAW264.7 cell line to investigate the effect and mechanism of alcohol on macrophages in colitis. Our study has found that alcohol exacerbates colitis in mice, increases the aggregation of colonic macrophages, and promotes the production of various inflammatory factors. Alcohol increases lipopolysaccharides (LPS)-induced calcium influx in macrophages, which is inhibited by the TRPV1 antagonist Capsazepine (CPZ). Alcohol and LPS together induce M2b polarization of macrophages and promote the phosphorylation and nuclear translocation of P38, ERK1/2 and NF-κB, and could be inhibited by CPZ and NOD2 inhibitor. Thus, alcohol can aggravate experimental colitis in mice and promote macrophage M2b polarization through the TRPV1-MAPK/NF-kB pathways.
2023-07-24 | GSE237785 | GEO
Project description:To examine the functional significance of TRPV1 SUMOylation in vivo, we created a TRPV1K823R KI transgenic mouse line.We thus performed gene expression profiling analysis using data obtained from RNA-seq of the trigeminal ganglion of TRPV1K823R and control mouse models . Our analyses unveiled a role for TRPV1 SUMOylation in regulating gene networks related to the pain and itch pathway.
2022-06-14 | GSE203197 | GEO
Project description:We developed an approach to rapidly eliminate the subgroup of sensory neurons expressing the heat-gated cation channel TRPV1 from dissociated rat sensory ganglia using agonist treatment followed by density centrifugation. To identify transcripts predominantly expressed in TRPV1-positive neurons, we compared the transcriptome of all cells within sensory ganglia versus all cells without TRPV1 expressing neurons using RNA-Seq.
2015-12-30 | E-MTAB-2789 | biostudies-arrayexpress
Project description:We developed an approach to rapidly eliminate the subgroup of sensory neurons expressing the heat-gated cation channel TRPV1 from dissociated rat sensory ganglia using agonist treatment followed by density centrifugation. To identify transcripts predomintly expressed in TRPV1-positive neurons, we compared the transcriptome of all cells within sensory ganglia versus all cells without TRPV1 expressing neurons using RNA-Seq. Four replicate experiments with RNA from DRG neurons of one rat per experiment were performed. Dissociated neurons were split up in three parts, treated with solvent DMSO (0.1%), casaicin (10 µM), or RTX (100 nM) for 30 min followed by gradient centrifugation. RNA was extracted from the remaining pellet containing either all cells or all cells without TRPV1-positive neurons.
2015-05-12 | E-GEOD-59727 | biostudies-arrayexpress
Project description:TRPV1 SUMOylation suppresses itch by inhibiting TRPV1 interaction with H1 receptors
| PRJNA838996 | ENA
Project description:Vampire bats and snakes have taken thermosensation to the extreme by developing specialized systems for detecting infrared radiation. As such, these creatures provide a window into the molecular and genetic mechanisms underlying evolutionary tuning of thermoreceptors in a species or cell type specific manner. In each case, robust thermal sensitivity likely reflects specialized anatomical features of infrared sensing pit organs, as well as intrinsic heat sensitivity of trigeminal nerve fibers that innervate these structures. Here we show that vampire bats use a molecular strategy involving alternative splicing of the TRPV1 gene to generate a channel specifically within trigeminal ganglia that has a reduced thermal activation threshold. Selective expression of splicing factors in trigeminal, but not dorsal root ganglia, together with unique organization of the vampire bat TRPV1 gene underlies this mechanism of sensory adaptation. Comparative genomic analysis of the TRPV1 locus supports phylogenetic relationships within the proposed Pegasoferae clade of mammals. Gene expression measurements implicate a TRPV1 splice isoform as the heat-sensitive channel in vampire bats
2011-08-04 | E-GEOD-28243 | biostudies-arrayexpress
Project description:We developed an approach to rapidly eliminate the subgroup of sensory neurons expressing the heat-gated cation channel TRPV1 from dissociated rat sensory ganglia using agonist treatment followed by density centrifugation. To identify transcripts predomintly expressed in TRPV1-positive neurons, we compared the transcriptome of all cells within sensory ganglia versus all cells without TRPV1 expressing neurons using RNA-Seq.
2015-05-12 | GSE59727 | GEO
Project description:Gastric cancer (GC) remains a significant health challenge due to its high mortality rate and the limited efficacy of current targeted therapies. A critical barrier in developing more effective treatments is the lack of understanding of specific mechanisms driving GC progression. This study investigates the role of Transient Receptor Potential Vanilloid 1 (TRPV1), a non-selective cation channel known for its high Ca2+ permeability and tumor-suppressive properties in gastrointestinal cancers. Specifically, we explore the impact of SUMOylation—a dynamic and reversible post-translational modification—on TRPV1's function in GC. We demonstrate that SUMOylation of TRPV1 inhibits cell proliferation and migration in MGC-803 and AGS gastric cancer cells. By mutating amino acids near TRPV1's existing SUMO motif (slKpE), we created a bidirectional SUMO motif (EψKψE) that enhances TRPV1 SUMOylation, resulting in further suppression of GC cell proliferation and migration. In vivo studies support these findings, showing that TRPV1 SUMOylation prevents spontaneous tumorigenesis in a mouse gastric cancer model. Further investigation reveals that TRPV1 SUMOylation increases the protein's membrane expression by inhibiting its interaction with the adaptor-related protein complex 2 mu 1 subunit (AP2M1). This elevated membrane expression leads to increased intracellular Ca2+ influx, activating the AMP-activated protein kinase (AMPK) pathway, which in turn inhibits the proliferation and migration of GC cells. In conclusion, our study elucidates a novel mechanism wherein TRPV1 SUMOylation promotes its membrane expression and activates the TRPV1-Ca2+-AMPK signaling pathway, thereby inhibiting GC cell proliferation and migration. These findings enhance our understanding of the molecular dynamics in gastric cancer and could provide a new theoretical basis for clinical treatment strategies.
2024-10-15 | GSE262378 | GEO
Project description:Given the inaccessibility of human sensory neurons (SNs), it is yet to be established whether the signalling pathway between histamine 1 receptor (H1R) and transient receptor potential cation channel subfamily V member 1 (TRPV1) is conserved between humans and mammalian models. Accessible human SNs are vital for identifying TRPV1 antagonists with higher potential for success in clinical trials targeting histaminergic itch, especially given TRPV1's species specificity concerns. Hence to build a humanized histamine-dependent itch model, we derived peripheral sensory neurons from human pluripotent stem cells (hiPSC-SNs) and validated channel functionality using immunostaining, calcium imaging and multielectrode array (MEA) recordings. Here, we demonstrated that a subset of hiPSC-SNs exhibits co-expression of H1R and TRPV1, responding to both histamine and capsaicin agonists. We found that inhibiting TRPV1 prevented histamine activation. Moreover, we show that silencing histamine-sensitive neurons reduces capsaicin response, and silencing capsaicin-sensitive neurons diminishes histamine response. To assess the ability of hiPSC-SNs in TRPV1 antagonist drug screening, we evaluated two well-established hyperthermic and three thermal-neutral TRPV1 antagonists. Our finding identifies SB366791, a thermal-neutral antagonist, as a potent inhibitor of H1R activation. The use of hiPSC-SNs may therefore provide a physiologically relevant means to perform large-scale screening to discover anti-pruritic agents predictive of actual efficacy in human clinical trials.
2024-02-27 | GSE256435 | GEO