Psoriasis is an immune-mediated chronic inflammatory skin disease characterized by erythema, scales, and infiltration of the skin, which causes deleterious effects on patient quality of life. TRP channel played important roles in the generation and conductance of itch signal . According to our results, psoriasis induced itch was TRPV4 dependent, and TRPV4 expression in both epidermis and DRG were up-regulated in psoriasis. Thus, TRPV4 is an attractive candidate for treating psoriasis induced itch. Cimifugin is a common compound in antipruritic Chinese medicine. In our study, GSK1016790A, a TRPV4 channel specific agonist, induced acute itch was inhibited by cimifugin in a dose-dependent manner. Furthermore, cimifugin treatment reduced the scratching behavior and reversed the TRPV4 up-regulation induced by psoriasis. In particular, cimifugin decreased GSK1016790A induced calcium response both in HaCaT cells and DRG neurons. Importantly, in TRPV4 transfected HEK293 cells, GSK101 induced calcium response was also significantly inhibited by cimifugin pretreatment. Consistent with our calcium imaging result, cimifugin pretreatment also inhibited GSK101 induced inward currents. Our study delineated a new role of TRPV4 in psoriasis and emphasized the antipruritic effect of cimifugin, which opened a new avenue to itch management in psoriasis.

牛皮癣是一种免疫介导的慢性炎症性皮肤病，其特征是皮肤出现红斑、鳞屑和浸润，对患者的生活质量造成有害影响。 TRP通道在痒信号的产生和传导中发挥着重要作用。根据我们的结果，银屑病引起的瘙痒是TRPV4依赖性的，并且银屑病中表皮和背根神经节中的TRPV4表达均上调。因此，TRPV4 是治疗银屑病引起的瘙痒的有吸引力的候选者。西米夫净是止痒中药中的常用复方。在我们的研究中，GSK1016790A（一种TRPV4通道特异性激动剂）引起的急性瘙痒被西米夫净以剂量依赖性方式抑制。此外，cimifugin 治疗减少了抓挠行为并逆转了银屑病引起的 TRPV4 上调。特别是，西米夫净降低了 HaCaT 细胞和 DRG 神经元中 GSK1016790A 诱导的钙反应。重要的是，在 TRPV4 转染的 HEK293 细胞中，GSK101 诱导的钙反应也被 cimifugin 预处理显着抑制。与我们的钙成像结果一致，西米夫净预处理也抑制了 GSK101 诱导的内向电流。我们的研究描绘了 TRPV4 在银屑病中的新作用，并强调了 cimifugin 的止痒作用，这为银屑病瘙痒治疗开辟了新途径。