The Role of Keratinocytes as Independent Thermosensors

角质形成细胞作为独立热传感器的作用

• 批准号: 7677676
• 负责人: Jaime Garcia-Anoveros
• 金额: $ 4.85万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-01 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7677676
• 关键词: Address; Affect; Afferent Neurons; Alleles; Blood flow; Body Temperature; Calcium; Cations; Cell Line; Cells; Data; Development; Disease; Eccrine Glands; Epidermis; Epithelial; Epithelial Cells; Epithelium; Esthesia; Family; Genes; Growth; Hair; Hair follicle structure; Heating; Human; Image; Knockout Mice; Labyrinth; Lead; Mediating; Melanosomes; Messenger RNA; Morphology; Mus; Nervous system structure; Perception; Physiological; Pigmentation physiologic function; Production; Proliferating; Regulation; Research; Role; Sensory; Skin; Skin Temperature; Spinal Ganglia; Staging; Stratum Basale; Sweat; Sweating; Temperature; Temperature Sense; Testing; Time; Universities; Variant; keratinocyte; keratinocyte differentiation; mouse model; patch clamp; peripheral blood; receptor; recombinase; response; skin disorder; warm temperature

Thermosensitive channels in skin keratinocytes and/or in sensory neurons innervating the skin open in response to heating or cooling and mediate our perception of ambient temperature. We have found that some basal epidermal cells, as well as matrix keratinocytes of the hair follicles, express the TRPML3 channel. We have also observed that this channel opens in response to changes in temperature that go from cold towards the homeostatic temperature of skin. Here we propose to address the following questions. (1) Which epithelial cells express TRPML3 channels, and at which stages of epidermal and folliclular epithelial development do these express these cation channels? (2) Do these cells display cold-to-warm thermosensitive currents and are these currents mediated by their endogenous TRPML3 channels? (3) Does TRPML3 elimination affect hair follicle or epidermal morphology? These studies aim at elucidating the function ofTRPML3 channels in the epidermis and hair follicle, and may lead to further studies of how the skin, including the vasculature and eccrine glands, detect and respond to changes in temperature.

皮肤角质形成细胞和/或神经支配皮肤的感觉神经元中的温度敏感通道在 对加热或冷却的反应，并调节我们对环境温度的感知。我们发现一些 基底表皮细胞以及毛囊的基质角质形成细胞表达TRPML 3通道。我们有 还观察到，这个通道打开响应温度的变化，从冷到热， 皮肤的稳态温度。在此，我们建议解决以下问题。(1)哪些上皮细胞 表达TRPML 3通道，以及在表皮和滤泡上皮发育的哪个阶段表达TRPML 3通道。 表达这些阳离子通道？(2)这些细胞是否显示由冷到暖的热敏电流， 由内源性TRPML 3通道介导的电流？(3)TRPML 3消除是否影响毛囊或 表皮形态这些研究旨在阐明TRPML 3通道在表皮中的功能， 毛囊，并可能导致进一步的研究如何皮肤，包括脉管系统和外分泌腺， 并对温度变化做出反应。