Qiu Yang, Tang Nan, Zhang Wen, Xiong Jian-Xia, Hu Li, Cai Tao
Department of Dermatology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Ann Palliat Med. 2020 Nov;9(6):3757-3765. doi: 10.21037/apm-20-1712. Epub 2020 Nov 10.
Lichen simplex chronicus (LSC) is an acquired chronic dermatosis that is often accompanied by severe paroxysmal pruritus, and its pathogenesis to date is still unclear. Transient receptor potential channel A1 (TRPA1) is a non-selective cation channel. TRPA1 is widely expressed in skin, sensory neurons, and various other tissues, along with various biological functions and activation mechanisms. This study aimed to explore the changes in TRPA1 expression in human LSC and provide evidence for further research on the role of TRPA1 in chronic pruritus.
A total of 21 skin lesion specimens from LSC patients with skin pruritus lasting more than 6 weeks, and 28 normal skin tissue specimens through the skin biopsy from June 2018 to February 2019 were collected. The expression of TRPA1 in these skin tissues was evaluated through western blotting, quantitative reverse transcription PCR (qRT-PCR), and immunohistochemical analysis. The changes of inflammatory mediators, including interleukin (IL)-6, IL-13, endothelin-1 (ET-1), and thymic stromal lymphopoietin (TSLP), as well as substance P, are also analyzed by qRT-PCR. TRPA1 was detected using immunohistochemistry for all skin layers, the basal layer, and around the blood vessels of the dermis.
The expression of TRPA1 in LSC specimens was significantly decreased as compared with that in the normal specimens (P<0.05). Also, TRPA1 protein levels were consistently decreased in LSC specimens (P<0.05). Simultaneously, the mRNA expressions of TRPA1, IL-6, IL-13, ET-1, TSLP, and substance P presented with no significant differences between LSC and normal specimens.
TRPA1 expression is proved downregulated in skin lesions of LSC patients with skin pruritus, indicating that TRPA1 serves as a crucial role in the pathogenesis of human LSC.
慢性单纯性苔藓(LSC)是一种后天性慢性皮肤病,常伴有严重的阵发性瘙痒,其发病机制至今仍不清楚。瞬时受体电位通道A1(TRPA1)是一种非选择性阳离子通道。TRPA1广泛表达于皮肤、感觉神经元和其他各种组织中,具有多种生物学功能和激活机制。本研究旨在探讨人LSC中TRPA1表达的变化,为进一步研究TRPA1在慢性瘙痒中的作用提供依据。
收集2018年6月至2019年2月期间通过皮肤活检获得的21例皮肤瘙痒持续超过6周的LSC患者的皮肤病变标本,以及28例正常皮肤组织标本。通过蛋白质免疫印迹法、定量逆转录聚合酶链反应(qRT-PCR)和免疫组织化学分析评估这些皮肤组织中TRPA1的表达。还通过qRT-PCR分析炎症介质白介素(IL)-6、IL-13、内皮素-1(ET-1)、胸腺基质淋巴细胞生成素(TSLP)以及P物质的变化。使用免疫组织化学方法检测所有皮肤层、基底层和真皮血管周围的TRPA1。
与正常标本相比,LSC标本中TRPA1的表达显著降低(P<0.05)。此外,LSC标本中TRPA1蛋白水平持续降低(P<0.05)。同时,LSC标本与正常标本之间TRPA1、IL-6、IL-13、ET-1、TSLP和P物质的mRNA表达无显著差异。
皮肤瘙痒的LSC患者皮肤病变中TRPA1表达下调,表明TRPA1在人LSC的发病机制中起关键作用。