UVB radiation generates sunburn pain and affects skin by activating epidermal TRPV4 ion channels and triggering endothelin-1 signaling
Open accessAbstract
At our body surface, the epidermis absorbs UV radiation. UV overexposure leads to sunburn with tissue injury and pain. To understand how, we focus on TRPV4, a nonselective cation channel highly expressed in epithelial skin cells and known to function in sensory transduction, a property shared with other transient receptor potential channels. We show that following UVB exposure mice with induced Trpv4 deletions, specifically in keratinocytes, are less sensitive to noxious thermal and mechanical stimuli than control animals. Exploring the mechanism, we find that epidermal TRPV4 orchestrates UVB-evoked skin tissue damage and increased expression of the proalgesic/algogenic mediator endothelin-1. In culture, UVB causes a direct, TRPV4-dependent Ca(2+) response in keratinocytes. In mice, topical treatment with a TRPV4-selective inhibitor decreases UVB-evoked pain behavior, epidermal tissue damage, and endothelin-1 expression. In humans, sunburn enhances epidermal expression of TRPV4 and endothelin-1, underscoring the potential of keratinocyte-derived TRPV4 as a therapeutic target for UVB-induced sunburn, in particular pain.
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Inhibiting TRPV4 expression can attenuate photoaging damage of epidermal cells and mouse skin, indicating potential of TRPV4 as a therapeutic target for photoaging.
“Inhibiting the expression of TRPV4 can attenuate photoaging damage of epidermal cells and mouse skin, indicating the potential of TRPV4 as a therapeutic target for photoaging [93].”
From Boosting the Photoaged Skin: The Potential Role of Dietary Components (2021) · cites this paper as [93]
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- Authors
- Moore, C., Cevikbas, F., Pasolli, H. A., Chen, Y., Kong, W., Kempkes, C., Parekh, P., Lee, S. H., Kontchou, N.-A., Yeh, I., Jokerst, N. M., Fuchs, E., Steinhoff, M., & Liedtke, W. B.
- Affiliations
- Liedtke Laboratory, Departments of Neurology and Neurobiology, and
- University of California, San Francisco (US)
- Fuchs Laboratory of Mammalian Cell Biology and Development and
- Duke University (US)
- Howard Hughes Medical Institute (US)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2013-08-08
- Volume
- 110
- Issue
- 34
- Pages
- E3225-34
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3752269
- OpenAlex
- W2160875760
- Cited by
- 259
- References
- 84
- Citations by year
- 2026: 17 · 2025: 20 · 2024: 15 · 2023: 20 · 2022: 18 · 2021: 28 · 2020: 26 · 2019: 14 · 2018: 11 · 2017: 24 · 2016: 22 · 2015: 15 · 2014: 25 · 2013: 3
- FWCI
- 12.49
- Type
- journal article
- Language
- en
- Update notices
- correction (2013-08-30)
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DukeSpace (Duke University) (submittedVersion, cc-by-nc-nd)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- Deutsche Forschungsgemeinschaft
- National Institutes of Health (2r01ar050452-21, AR050452)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR050452, R01AR059402, AR 31737, AR059402, R01AR031737, R01-AR050452)
- National Institute of Biomedical Imaging and Bioengineering (P41EB015897)
- National Institute of Dental and Craniofacial Research (DE018549, DE018549S2, DE018549S1, R01DE018549)
- Topics
- Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Health Sciences › Medicine › Dermatology › Skin Protection and Aging
- Keywords
- UV-B radiation, TRPV4, endothelin-1, keratinocytes, epidermis, TRP channels, thermal and mechanical nociception, calcium signaling, photodermatosis
- MeSH terms
- Analysis of Variance, Animals, Cells, Cultured, Epithelial Cells, Immunohistochemistry, Mice, Transgenic, Microscopy, Electron, Pain, Skin, Sunburn, Ultraviolet Rays, Signal Transduction, Endothelin-1, TRPV Cation Channels, Mice
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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