Department of Dermatology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China; Department of Dermatology, Binzhou Medical University Hospital, Binzhou, China.
Department of Dermatology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.
J Invest Dermatol. 2022 Nov;142(11):2978-2987.e6. doi: 10.1016/j.jid.2022.04.014. Epub 2022 May 2.
It is well known that psoriasis is closely related to smoking, and CHRNA5 plays an important role in smoking-related diseases. However, studies on the relationship between CHRNA5 and psoriasis are limited. This study aimed to examine the role of CHRNA5 in psoriasis development and pathogenesis. Analysis in psoriatic tissues and imiquimod-induced mouse models showed that CHRNA5 was highly expressed in psoriatic lesional skin. To further verify the function of CHRNA5, we constructed Chrna5-knockout mice and induced the psoriasis model. We found that Chrna5 knockout significantly reduced the severity of psoriasis and could regulate inflammation through the MAPK kinase kinase-1/c-Jun N-terminal kinase‒MAPK/NF-κB pathway. The single-cell sequencing results revealed that after Chrna5 knockout, the keratinocyte subpopulation was significantly reduced and the related Jak/signal transducer and activator of transcription signaling pathway was downregulated, further indicating the importance of CHRNA5 in psoriasis. Human keratinocytes were analyzed, and silencing CHRNA5 inhibited keratinocyte proliferation and migration. In summary, CHRNA5 played important roles in the development and pathogenesis of psoriasis, and targeting CHRNA5 may be an effective strategy for the treatment of psoriasis.
众所周知，银屑病与吸烟密切相关，CHRNA5 在与吸烟相关的疾病中发挥着重要作用。然而，关于 CHRNA5 与银屑病的关系的研究有限。本研究旨在探讨 CHRNA5 在银屑病发病机制中的作用。对银屑病组织和咪喹莫特诱导的小鼠模型的分析表明，CHRNA5 在银屑病皮损皮肤中高度表达。为了进一步验证 CHRNA5 的功能，我们构建了 Chrna5 敲除小鼠并诱导了银屑病模型。我们发现 Chrna5 敲除显著减轻了银屑病的严重程度，并可通过 MAPK 激酶激酶-1/c-Jun N-末端激酶-MAPK/NF-κB 通路调节炎症。单细胞测序结果表明，Chrna5 敲除后，角蛋白细胞亚群显著减少，相关 Jak/信号转导和转录激活因子信号通路下调，进一步表明 CHRNA5 在银屑病中的重要性。分析人角质形成细胞，沉默 CHRNA5 抑制角质形成细胞增殖和迁移。总之，CHRNA5 在银屑病的发生和发病机制中发挥着重要作用，靶向 CHRNA5 可能是治疗银屑病的有效策略。
