ArticleGastroenterology2021
Epithelia-Sensory Neuron Cross Talk Underlies Cholestatic Itch Induced by Lysophosphatidylcholine.
Article in Gastroenterology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
What it found
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The trial behind it
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Who cites it
47 citing papers in PubMed, 85 citations in OpenAlex.
- The basolateral amygdala decodes visceral pain and itch via distinct circuits and molecules.Nature communications · 2026Article
- 25+ Years of TRPV4: From Discovery to Translational Horizons.Research square · 2026Article
- Elevated 18:1 lysophosphatidylcholine contributes to neuropathic pain in peripheral nerve injury.Regional anesthesia and pain medicine · 2026Article
- TRPV4-Mast Cell Interactions in Neurogenic Inflammation and Chronic Diseases: A Narrative Review.International journal of molecular sciences · 2026Review
- Variation in microbiome and metabolites is associated with advantageous effects of cholestyramine on primary biliary cholangitis with pruritus.Microbiology spectrum · 2026Article
- New and emerging treatments for PBC-related pruritus.Drugs in context · 2026Review
- Lysophosphatidylcholine sensitizes TRPV2 by indirect mechanisms.Pflugers Archiv : European journal of physiology · 2025Article
- Neuronal Mechanisms of Psoriatic Itch: Role of IL-17R/ERK/TRPV4 Signaling Pathway.The Journal of investigative dermatology · 2025Article
- Osmotic pressure-induced calcium response states.FEBS open bio · 2025Article
- Molecular and cellular mechanisms of itch sensation and the anti-itch drug targets.Acta pharmacologica Sinica · 2025Review
- Article
- A QUARTER CENTURY OF CALCIUM-PERMEABLE ION CHANNEL, TRPV4: PERSPECTIVES ON EXPRESSION AND FUNCTION IN ENDOTHELIAL CELLS-TIME TO TRANSLATE.Transactions of the American Clinical and Climatological Association · 2025Review
- Advances in the Study for Modulators of Transient Receptor Potential Vanilloid (TRPV) Channel Family.Current topics in medicinal chemistry · 2025Review
- Lysophosphatidylcholine induced by fat transplantation regulates hyperalgesia by affecting the dysfunction of ACC perineuronal nets.iScience · 2024Article
- Recent advances on the structure and the function relationships of the TRPV4 ion channel.Channels (Austin, Tex.) · 2024Review
- Review
- Identification and Properties of TRPV4 Mutant Channels Present in Polycystic Kidney Disease Patients.Function (Oxford, England) · 2024Article
- TRPV Channels in Osteoarthritis: A Comprehensive Review.Biomolecules · 2024Review
- Site-Specific Transient Receptor Potential Channel Mechanisms and Their Characteristics for Targeted Chronic Itch Treatment.Biomolecules · 2024Review
- An update on mechanisms of pruritus and their potential treatment in primary cutaneous T-cell lymphoma.Clinical and experimental medicine · 2023Review
Corrections and comments
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Authors and funding
27 authors at 7 institutions in 4 countries.
Funding
Abstract
BACKGROUND &
aimsLimited understanding of pruritus mechanisms in cholestatic liver diseases hinders development of antipruritic treatments. Previous studies implicated lysophosphatidic acid (LPA) as a potential mediator of cholestatic pruritus.
methodsPruritogenicity of lysophosphatidylcholine (LPC), LPA's precursor, was examined in naïve mice, cholestatic mice, and nonhuman primates. LPC's pruritogenicity involving keratinocyte TRPV4 was studied using genetic and pharmacologic approaches, cultured keratinocytes, ion channel physiology, and structural computational modeling. Activation of pruriceptor sensory neurons by microRNA-146a (miR-146a), secreted from keratinocytes, was identified by in vitro and ex vivo Ca
resultsLPC was robustly pruritic in mice. TRPV4 in skin keratinocytes was essential for LPC-induced itch and itch in mice with cholestasis. Three-dimensional structural modeling, site-directed mutagenesis, and channel function analysis suggested a TRPV4 C-terminal motif for LPC binding and channel activation. In keratinocytes, TRPV4 activation by LPC induced extracellular release of miR-146a, which activated TRPV1
conclusionsWe identified LPC as a novel cholestatic pruritogen that induces itch through epithelia-sensory neuron cross talk, whereby it directly activates skin keratinocyte TRPV4, which rapidly releases miR-146a to activate skin-innervating TRPV1
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.