NB-UVB irradiation downregulates keratin-17 expression in keratinocytes by inhibiting the ERK1/2 and STAT3 signaling pathways
NB-UVB irradiation downregulates keratin-17 expression in keratinocytes by inhibiting the ERK1/2 and STAT3 signaling pathways
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NB-UVB 照射通过抑制 ERK1/2 和 STAT3 信号通路下调角质形成细胞中 keratin-17 的表达
DOI：
10.1007/s00403-018-1812-1
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发表时间：
2018-03-01
影响因子：
3
通讯作者：
Wang, Gang
中科院分区：
文献类型：
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作者：
Zhuang, Yuchen;Han, Changxu;Wang, Gang
Keratin-17 (K17) 是一种由角质形成细胞 (KC) 产生的细胞骨架蛋白，在银屑病中过度表达，可能在其发病机制中发挥关键作用。窄带紫外线 B (NB-UVB) 照射被用作银屑病的一般治疗方法，但其对 K17 表达的影响尚未确定。本研究旨在探讨NB-UVB照射对K17表达及其信号通路的影响。暴露于 NB-UVB 照射后，通过流式细胞术、CCK-8 测定和透射电子显微镜对永生化人角质形成细胞（HaCaT 细胞）进行分析，以检查增殖情况。同时，通过实时定量聚合酶链式反应（qRT-PCR）、蛋白质印迹分析和免疫荧光检测原代人上皮角质形成细胞中K17的表达。对与 PD-98059 和白皮杉醇预孵育的 HaCaT 细胞进行蛋白质印迹分析，以检查 ERK1/2 和 STAT3 磷酸化。取用咪喹莫特 (IMQ) 处理并经 NB-UVB 照射的小鼠耳朵，通过 qRT-PCR、蛋白质印迹分析和免疫荧光检查 K17 表达。结果表明，400 mJ/cm(2)的NB-UVB照射是HaCaT细胞的最大耐受剂量，可抑制HaCaT细胞增殖并适度增加早期凋亡。此外，NB-UVB 照射可以通过抑制 ERK1/2 和 STAT3 信号通路来下调 K17 表达。在体内实验中，MED或更高剂量的NB-UVB照射可以消除IMQ诱导的银屑病样皮炎并抑制K17表达。这些结果表明，NB-UVB 照射可能通过 ERK1/2 和 STAT3 信号通路抑制 K17 表达来消除慢性银屑病斑块。
Keratin-17 (K17) is a cytoskeletal protein produced by keratinocytes (KCs), which is overexpressed in psoriasis and may play a pivotal role in its pathogenesis. Narrow-band ultraviolet B (NB-UVB) irradiation is used as a general treatment for psoriasis, although its impact on K17 expression has yet to be determined. In this study, we aimed to investigate the effect of NB-UVB irradiation on K17 expression and its signaling pathways. After exposure to NB-UVB irradiation, immortalized human keratinocytes (HaCaT cells) were analyzed by flow cytometry, CCK-8 assays and transmission electron microscopy to examine proliferation. Meanwhile, K17 expression in primary human epithelial keratinocytes was detected by quantitative real-time polymerase chain reaction (qRT-PCR), western blot analysis and immunofluorescence. HaCaT cells pre-incubated with PD-98059 and piceatannol were subjected to western blot analysis to examine ERK1/2 and STAT3 phosphorylation. The ears of mice treated with imiquimod (IMQ) and irradiated by NB-UVB were taken to examine K17 expression by qRT-PCR, western blot analysis, and immunofluorescence. Our results showed that 400 mJ/cm(2) of NB-UVB irradiation was the maximum tolerable dose for HaCaT cells and could cause inhibited HaCaT cell proliferation and moderate increase of the early apoptosis. Furthermore, NB-UVB irradiation could downregulate K17 expression by inhibiting the ERK1/2 and STAT3 signaling pathways. In experiments conducted in vivo, NB-UVB irradiation with doses of MED or higher could eliminate the IMQ-induced psoriasis-like dermatitis and inhibit K17 expression. These results indicated that NB-UVB irradiation may eliminate chronic psoriatic plaques by suppressing K17 expression via the ERK1/2 and STAT3 signaling pathways.