银屑病发病广泛，严重影响患者的健康。目前的治疗手段不能满足临床需求，因此，发现治疗银屑病的新靶点并发现作用于这一靶点的新颖药物具有广泛的理论价值及临床意义。TRPV3主要在皮肤角质形成细胞（KC）表达，参与炎症反应。本课题提出KC中的TRPV3是一个调控银屑病的关键分子，并可作为分子靶点来开发治疗银屑病药物的假说。本课题将通过生物学、药理学、电生理学的方法，利用咪喹莫特诱导的银屑病动物模型来证明KC中的TRPV3是调控银屑病的关键分子；利用原代培养KC考察TRPV3调控趋化因子的释放及细胞增殖，阐明TRPV3调控银屑病的初步机制；通过高通量药物筛选发现TRPV3选择性抑制剂并验证其对银屑病的治疗效果。本课题的顺利实施，有望进一步阐明银屑病的病理机制，证明KC中的TRPV3对银屑病的调控作用；有望发现治疗银屑病的分子靶点；同时有望发现TRPV3的特异性抑制剂，为治疗银屑病提供先导分子。

Psoriasis approximately affects 1.5-2% population worldwide and severely influences patients’ health with unmet therapeutic interventions. Therefore, further studies to investigate the pathological mechanisms which are responsible for psoriasis progression and unravel novel molecular targets for developing therapeutic interventions are of significance to both basic research and clinic application. It has been reported that Transient Receptor Potential cation channel, subfamily V, member 3 (TRPV3) is abundantly expressed in epidermal keratinocytes and regulating a variety of physiological function of skin, including barrier formation, epithelial injury recovery and release of a plethora of proinflammatory mediators, cytokines as well as chemokines therefore amplifying inflammation in the skin to aggravate psoriasis. In this study, we hypothesize that TRPV3 is a key regulator of psoriasis progression and can served as a molecular target to discover the drugs for psoriasis treatment. In this study, combined with pharmacological, biological as well as electrophysiological approaches, we will investigate the relationship between TRPV3 and psoriasis to demonstrate that TRPV3 expressed in keratinocytes is a critical regulator for psoriasis progression using imiquimod-induced psoriatic lesion mouse model. We will further investigate whether and how TRPV3 regulating the release of cytokines, chemokines and proinflammatory mediators in primary cultured keratinocytes to elucidate the molecular mechanisms for TRPV3 regulating psoriasis. Moreover, we will apply high throughput approaches to discover TRPV3 selective inhibitor(s) and characterize the gating property of TRPV3 inhibitor(s). Finally, we will evaluate the efficacy of discovered TRPV3 inhibitor(s) in psoriatic mouse model. Our study will further elucidate the key role of TRPV3 in psoriasis progression and demonstrate that TRPV3 is a druggable target for development of treatment for psoriasis. We will also discover TRPV3 selective inhibitor(s) which not only can serve as a molecular probe to unravel the patho-physiological function of TRPV3 but also may serve as a lead compound to develop the treatment for psoriasis.