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TRPV1 SUMOylation suppresses itch by inhibiting TRPV1 interaction with H1 receptors

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE203197 | GEO | 2022/06/14

REPOSITORIES: GEO

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TRPV1 SUMOylation suppresses itch by inhibiting TRPV1 interaction with H1 receptors

Project description:TRPV1 SUMOylation suppresses itch by inhibiting TRPV1 interaction with H1 receptors

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SUMOylation-Induced Membrane Localization of TRPV1 Suppresses Proliferation and Migration in Gastric Cancer Cells

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Alternative splicing of the TRPV1 gene underlies infrared sensation in vampire bats

2011-08-04 | GSE28243 | GEO

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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.

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2020-03-01 | E-MTAB-8273 | biostudies-arrayexpress

RNA-seq of splenic B cells derived from WT and Itch cKO mice

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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.

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