UVB radiation generates sunburn pain and affects skin by activating epidermal TRPV4 ion channels and triggering endothelin-1 signaling
- 8 August 2013
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 110 (34), E3225-E3234
- https://doi.org/10.1073/pnas.1312933110
Abstract
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.Keywords
This publication has 84 references indexed in Scilit:
- NFIB is a governor of epithelial–melanocyte stem cell behaviour in a shared nicheNature, 2013
- TRPV1-lineage neurons are required for thermal sensationThe EMBO Journal, 2010
- The TRPV4 Channel Contributes to Intercellular Junction Formation in KeratinocytesPublished by Elsevier BV ,2010
- Ablation of TrpV1 neurons reveals their selective role in thermal pain sensationMolecular and Cellular Neuroscience, 2010
- The Ion Channel TRPA1 Is Required for Normal Mechanosensation and Is Modulated by Algesic StimuliGastroenterology, 2009
- Epidermal progenitors give rise to Merkel cells during embryonic development and adult homeostasisThe Journal of cell biology, 2009
- TRPV1-expressing primary afferents generate behavioral responses to pruritogens via multiple mechanismsProceedings of the National Academy of Sciences of the United States of America, 2009
- Finding One's Niche in the SkinCell Stem Cell, 2009
- Endothelin Receptors and PainThe Journal of Pain, 2009
- Association of catastrophizing with interleukin-6 responses to acute painPain, 2008