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UVB radiation generates sunburn pain and affects skin by activating epidermal TRPV4 ion channels and triggering endothelin-1 signaling.

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Date
2013-08-20
Authors
Moore, Carlene
Cevikbas, Ferda
Pasolli, H Amalia
Chen, Yong
Kong, Wei
Kempkes, Cordula
Parekh, Puja
Lee, Suk Hee
Kontchou, Nelly-Ange
Yeh, Iwei
Jokerst, Nan Marie
Fuchs, Elaine
Steinhoff, Martin
Liedtke, Wolfgang B
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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 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.
Type
Journal article
Subject
calcium-permeable channels
epithelial–neuronal cross-talk
photodermatitis
phototransduction
Analysis of Variance
Animals
Cells, Cultured
Endothelin-1
Epithelial Cells
Immunohistochemistry
Mice
Mice, Transgenic
Microscopy, Electron
Pain
Signal Transduction
Skin
Sunburn
TRPV Cation Channels
Ultraviolet Rays
Permalink
https://hdl.handle.net/10161/12972
Published Version (Please cite this version)
10.1073/pnas.1312933110
Publication Info
Moore, Carlene; Cevikbas, Ferda; Pasolli, H Amalia; Chen, Yong; Kong, Wei; Kempkes, Cordula; ... Liedtke, Wolfgang B (2013). UVB radiation generates sunburn pain and affects skin by activating epidermal TRPV4 ion channels and triggering endothelin-1 signaling. Proc Natl Acad Sci U S A, 110(34). pp. E3225-E3234. 10.1073/pnas.1312933110. Retrieved from https://hdl.handle.net/10161/12972.
This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.
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Scholars@Duke

Chen

Yong Chen

Associate Professor in Neurology
Jokerst

Nan Marie Jokerst

J. A. Jones Distinguished Professor of Electrical and Computer Engineering
Dr. Nan Marie Jokerst is the J. A. Jones Distinguished Professor of Electrical and Computer Engineering at Duke University, and the Executive Director of the Duke Shared Materials Instrumentation Facility, a Duke shared cleanroom and characterization facility. She received her BS in Physics from Creighton University in 1982, and her MS and PhD in Electrical Engineering from the University of Southern California in 1984 and 1989, respectively. She is a Fellow of the IEEE, and has served as an el
Liedtke

Wolfgang Bernhard Liedtke

Adjunct Professor in the Department of Neurology
Research Interests in the Liedtke-Lab: Pain/ nociception Sensory transduction and -transmission TRP ion channels Water and salt equilibrium regulated by the central nervous system Visit the lab's website, download papers and read Dr. Liedtke's CV here.
Moore

Carlene D Moore

Assistant Professor in Neurology
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