UVB radiation generates sunburn pain and affects skin by activating epidermal TRPV4 ion channels and triggering endothelin-1 signaling.
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.
Liedtke Laboratory, Departments of Neurology and Neurobiology, and Jokerst Laboratory, Department of Electrical Engineering, Duke University, Durham, NC 27710, USA.
Carlene
C
Moore
Ferda
F
Cevikbas
H Amalia
HA
Pasolli
Yong
Y
Chen
Wei
W
Kong
Cordula
C
Kempkes
Puja
P
Parekh
Suk Hee
SH
Lee
Nelly-Ange
NA
Kontchou
Iwei
I
Yeh
Iwei
I
Ye
Nan Marie
NM
Jokerst
Elaine
E
Fuchs
Martin
M
Steinhoff
Wolfgang B
WB
Liedtke
D000704:Analysis of Variance; D000818:Animals; D002478:Cells, Cultured; D019332:Endothelin-1 / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism / Q000528:radiation effects*; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D008854:Microscopy, Electron; D010146:Pain / Q000209:etiology / Q000378:metabolism*; D015398:Signal Transduction / Q000528:radiation effects*; D012867:Skin / Q000166:cytology; D013471:Sunburn / Q000378:metabolism* / Q000473:pathology; D050916:TRPV Cation Channels / Q000378:metabolism*; D014466:Ultraviolet Rays
D019332:Endothelin-1; D050916:TRPV Cation Channels; C486576:Trpv4 protein, mouse
calcium-permeable channels; epithelial–neuronal cross-talk; photodermatitis; phototransduction