Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 110, Issue 34, Pages E3225-E3234Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1312933110
Keywords
calcium-permeable channels; epithelial-neuronal cross-talk; photodermatitis; phototransduction
Categories
Funding
- National Institutes of Health (NIH)/National Institute of Dental and Craniofacial Research [DE018549, DE018549S1, DE018549S2]
- NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) [AR059402]
- Deutsche Forschugsgemeinschaft [German Research Foundation
- DFG] [STE 1014/2-2, DFG Ce165/1-1, DFG Ke1672/1-1]
- NIH/NIAMS [AR31737, AR050452]
- NIH/National Institute of Biomedical Imaging and Bioengineering [P41 EB015897]
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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 Ca2+ 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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