UVB radiation generates sunburn pain and affects skin by activating epidermal TRPV4 ion channels and triggering endothelin-1 signaling
UVB radiation generates sunburn pain and affects skin by activating epidermal TRPV4 ion channels and triggering endothelin-1 signaling
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DOI：
10.1073/pnas.1312933110
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发表时间：
2013-08-20
影响因子：
11.1
通讯作者：
Liedtke, Wolfgang B.
中科院分区：
文献类型：
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作者：
Moore, Carlene;Cevikbas, Ferda;Liedtke, Wolfgang B.
在我们的身体表面，表皮吸收紫外线辐射。紫外线过度照射会导致晒伤，并伴有组织损伤和疼痛。为了了解如何，我们专注于TRPV 4，一种在上皮皮肤细胞中高度表达的非选择性阳离子通道，已知在感觉转导中起作用，这是与其他瞬时受体电位通道共享的特性。我们发现，UVB照射诱导Trpv 4缺失的小鼠，特别是在角质形成细胞，是不太敏感的伤害性热和机械刺激比对照组动物。探索机制，我们发现，表皮TRPV 4编排UVB引起的皮肤组织损伤和增加的表达的proalgesic/algogenic介质内皮素-1。在培养中，UVB引起角质形成细胞中直接的TRPV 4依赖性Ca 2+反应。在小鼠中，用TRPV 4选择性抑制剂局部治疗可降低UVB诱发的疼痛行为、表皮组织损伤和内皮素-1表达。在人类中，晒伤增强了TRPV 4和内皮素-1的表皮表达，强调了角质形成细胞衍生的TRPV 4作为UVB诱导的晒伤，特别是疼痛的治疗靶点的潜力。
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.