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

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.

Department

Description

Provenance

Citation

Published Version (Please cite this version)

10.1073/pnas.1312933110

Publication Info

Moore, Carlene, Ferda Cevikbas, H Amalia Pasolli, Yong Chen, Wei Kong, Cordula Kempkes, Puja Parekh, Suk Hee Lee, et al. (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.

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Scholars@Duke

Moore

Carlene D Moore

Assistant Professor in Neurology
Chen

Yong Chen

Associate Professor in Neurology

Dr. Yong Chen is an Associate Professor of Neurology at the Duke University School of Medicine.  He is also affiliated with Duke Anesthesiology-Center for Translational Pain Medicine (CTPM) and Duke-Pathology.

The Chen lab mainly studies sensory neurobiology of pain and itch, with a focus on TRP ion channels and neural circuits. The main objective of our lab is to identify molecular and cellular mechanisms underlying chronic pain and chronic-disease associated itch, using a combination of animal behavioral, genetic, molecular and cellular, advanced imaging, viral, and optogenetic approaches.  There are three major research areas in the lab: craniofacial pain, arthritis pain and joint function, and systemic-disease associated itch.

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 elected member of the IEEE LEOS Board of Governors, and as the VP for Conferences and as the VP Technical Affairs. She is a Fellow of the Optical Society of America, and has served as Chair of the OSA Engineering Council. Her awards include an NSF Presidential Young Investigator Award, an IEEE Third Millenium Medal, the IEEE/HP Harriet B. Rigas Medal, and the Alumni in Academia Award for the University of Southern California Viterbi School of Engineering. She currently serves on the National Academies Board on Global Science and Technology. She has published over 200 refereed journal and conference publications, and has 6 patents.

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.

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