Yan Jinjin, Ye Fan, Ju Ying, Wang Dijun, Chen Jiao, Zhang Xinyu, Yin Zhi, Wang Changming, Yang Yan, Zhu Chan, Zhou Yuan, Cao Peng, Xu Yang, Yu Guang, Tang Zongxiang
School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023 China.
Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China; Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, China.
Cell Calcium. 2021 May 25;97:102429. doi: 10.1016/j.ceca.2021.102429.
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.
银屑病是一种免疫介导的慢性炎症性皮肤病，其特征为皮肤红斑、鳞屑及浸润，对患者生活质量产生有害影响。瞬时受体电位（TRP）通道在瘙痒信号的产生和传导中起重要作用。根据我们的研究结果，银屑病诱发的瘙痒依赖于瞬时受体电位香草酸亚型4（TRPV4），且银屑病患者表皮和背根神经节（DRG）中的TRPV4表达均上调。因此，TRPV4是治疗银屑病诱发瘙痒的一个有吸引力的候选靶点。升麻素苷是一种常见的止痒中药成分。在我们的研究中，TRPV4通道特异性激动剂GSK1016790A诱发的急性瘙痒被升麻素苷以剂量依赖的方式抑制。此外，升麻素苷治疗减少了搔抓行为，并逆转了银屑病诱导的TRPV4上调。特别是，升麻素苷降低了GSK1016790A在人永生化角质形成细胞（HaCaT细胞）和DRG神经元中诱导的钙反应。重要的是，在转染了TRPV4的人胚肾293（HEK293）细胞中，升麻素苷预处理也显著抑制了GSK101诱导的钙反应。与我们的钙成像结果一致，升麻素苷预处理也抑制了GSK101诱导的内向电流。我们的研究揭示了TRPV4在银屑病中的新作用，并强调了升麻素苷的止痒作用，这为银屑病瘙痒的治疗开辟了一条新途径。
