ArticleThe Journal of biological chemistry2016
Transient Receptor Potential Vanilloid 4 Ion Channel Functions as a Pruriceptor in Epidermal Keratinocytes to Evoke Histaminergic Itch.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.
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Who cites it
75 citing papers in PubMed, 135 citations in OpenAlex.
- TRPV4 Regulates Imiquimod (IMQ)-Induced Psoriasis via CaMKKβ/AMPK and Calmodulin/Akt-Mediated Autophagic Signaling Pathways in Juvenile Murine Keratinocytes.Dermatopathology (Basel, Switzerland) · 2026Article
- Mechanisms of pruritus and advances in traditional Chinese medicine therapy (Review).Molecular medicine reports · 2026Review
- 25+ Years of TRPV4: From Discovery to Translational Horizons.Research square · 2026Article
- From neuroimmune circuits to targeted therapy of chronic pruritus.Pharmacological reviews · 2026Review
- Modulation of Nociceptive Ion Channels by Protease-Activated Receptor-2 in Inflammatory Pain: Molecular Mechanisms and Therapeutic Potential.International journal of molecular sciences · 2026Review
- Transient Receptor Potential (TRP) Channels as Fundamental Regulators of Fibrosis and Pruritus-A New Therapeutic Target for Pathological Scar Management.International journal of molecular sciences · 2026Review
- Itching, Ionic Channels, Immune System, Magnesium and Antioxidants.Clinical, cosmetic and investigational dermatology · 2026Review
- A Hot-Spring Water Improves Inflammatory Conditions in an Injury-Induced Atopic Dermatitis Mouse Model by Regulating Skin Barrier Function.Biomedicines · 2025Article
- Neuronal Mechanisms of Psoriatic Itch: Role of IL-17R/ERK/TRPV4 Signaling Pathway.The Journal of investigative dermatology · 2025Article
- Heat-off responses of epidermal cells sensitizebioRxiv : the preprint server for biology · 2025Article
- The Influence of Retinol Ointment on Rabbit Skin (International journal of molecular sciences · 2024Article
- LPS exacerbates TRPV4-mediated itch through the intracellular TLR4-PI3K signalling.Journal of cellular and molecular medicine · 2024Article
- Cimifugin Relieves Histamine-Independent Itch in Atopic Dermatitis via Targeting the CQ Receptor MrgprA3.ACS omega · 2024Article
- Site-Specific Transient Receptor Potential Channel Mechanisms and Their Characteristics for Targeted Chronic Itch Treatment.Biomolecules · 2024Review
- Regulation of Neural Functions by Brain Temperature and Thermo-TRP Channels.Advances in experimental medicine and biology · 2024Review
- Involvement of the Transient Receptor Channels in Preclinical Models of Musculoskeletal Pain.Current neuropharmacology · 2024Review
- Targeting Transient Receptor Potential (TRP) Channels, Mas-Related G-Protein-Coupled Receptors (Mrgprs), and Protease-Activated Receptors (PARs) to Relieve Itch.Pharmaceuticals (Basel, Switzerland) · 2023Review
- An update on mechanisms of pruritus and their potential treatment in primary cutaneous T-cell lymphoma.Clinical and experimental medicine · 2023Review
- Alleviation of allergic conjunctivitis by (±)5(6)-dihydroxy-8Z,11Z,14Z,17Z-eicosatetraenoic acid in mice.Frontiers in pharmacology · 2023Article
- Pruritogenic molecules in the skin of patients with dermatomyositis.Frontiers in medicine · 2023Article
15 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
TRPV4 ion channels function in epidermal keratinocytes and in innervating sensory neurons; however, the contribution of the channel in either cell to neurosensory function remains to be elucidated. We recently reported TRPV4 as a critical component of the keratinocyte machinery that responds to ultraviolet B (UVB) and functions critically to convert the keratinocyte into a pain-generator cell after excess UVB exposure. One key mechanism in keratinocytes was increased expression and secretion of endothelin-1, which is also a known pruritogen. Here we address the question of whether TRPV4 in skin keratinocytes functions in itch, as a particular form of "forefront" signaling in non-neural cells. Our results support this novel concept based on attenuated scratching behavior in response to histaminergic (histamine, compound 48/80, endothelin-1), not non-histaminergic (chloroquine) pruritogens in Trpv4 keratinocyte-specific and inducible knock-out mice. We demonstrate that keratinocytes rely on TRPV4 for calcium influx in response to histaminergic pruritogens. TRPV4 activation in keratinocytes evokes phosphorylation of mitogen-activated protein kinase, ERK, for histaminergic pruritogens. This finding is relevant because we observed robust anti-pruritic effects with topical applications of selective inhibitors for TRPV4 and also for MEK, the kinase upstream of ERK, suggesting that calcium influx via TRPV4 in keratinocytes leads to ERK-phosphorylation, which in turn rapidly converts the keratinocyte into an organismal itch-generator cell. In support of this concept we found that scratching behavior, evoked by direct intradermal activation of TRPV4, was critically dependent on TRPV4 expression in keratinocytes. Thus, TRPV4 functions as a pruriceptor-TRP in skin keratinocytes in histaminergic itch, a novel basic concept with translational-medical relevance.
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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.