Notch-1 intervenes in the reparative processes of mucosa by controlling cell proliferation, differentiation and stem cell maintenance. Cigarette smoke alters airway epithelial homeostasis. The present study explored whether: Smokers showed altered Notch-1 expression; and whether in bronchial epithelial cells (16HBE): a) cigarette smoke extracts (CSE) altered the expression of Notch-1, of its ligand Jagged-1 (Jag-1) and the nuclear translocation of Notch-1; b) Notch-1 signaling activation as well as CSE modified Ki67, PCNA, p21, IL-33 expression, cell proliferation and repair processes. Notch-1 expression was assessed in the epithelium from large airway surgical samples from non-smoker and smoker subjects by immunohistochemistry.16HBE were cultured with/without CSE and Jag-1. A Notch-1 inhibitor (DAPT) was used as control. The expression of Notch-1, Jag-1, Ki67, PCNA, p21, IL-33 and cell proliferation (by CFSE) were all assessed by flow cytometry. Notch-1 nuclear expression was evaluated by immunofluorescence and western blot analysis. Repair processes were assessed by wound assay. Smokers had cytoplasmic but not nuclear Notch-1 expression. Although CSE increased Notch-1 expression, it counteracted Notch-1 signaling activation since it reduced Jag-1 expression and Notch-1 nuclear translocation. Notch-1 signaling activation by Jag-1 increased Ki67, PCNA and repair processes but reduced intracellular IL-33 and p21 expression without affecting cell proliferation. DAPT counteracted the effects of Notch-1 activation on PCNA and IL-33. CSE increased Ki67, PCNA, p21 and IL-33 expression but reduced cell proliferation and repair processes. In conclusion, cigarette smoke exposure, limiting Notch-1 signaling activation and hindering repair processes, amplifies injury processes in bronchial epithelial cells.

中文翻译：

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Notch-1 信号激活受损阻碍暴露于香烟烟雾的支气管上皮细胞的修复过程

Notch-1 通过控制细胞增殖、分化和干细胞维持来干预粘膜的修复过程。香烟烟雾改变气道上皮稳态。本研究探讨是否： 吸烟者表现出改变的 Notch-1 表达；以及是否在支气管上皮细胞 (16HBE) 中：a) 香烟烟雾提取物 (CSE) 改变了 Notch-1、其配体 Jagged-1 (Jag-1) 的表达和 Notch-1 的核易位；b) Notch-1 信号激活以及 CSE 修饰的 Ki67、PCNA、p21、IL-33 表达、细胞增殖和修复过程。Notch-1 表达在来自非吸烟者和吸烟者受试者的大气道手术样本的上皮中通过免疫组织化学评估。16HBE 在有/没有 CSE 和 Jag-1 的情况下培养。Notch-1 抑制剂 (DAPT) 用作对照。Notch-1的表达，Jag-1、Ki67、PCNA、p21、IL-33 和细胞增殖（通过 CFSE）均通过流式细胞术进行评估。Notch-1 核表达通过免疫荧光和蛋白质印迹分析进行评估。通过伤口分析评估修复过程。吸烟者具有细胞质而非核 Notch-1 表达。虽然 CSE 增加了 Notch-1 的表达，但它抵消了 Notch-1 信号激活，因为它减少了 Jag-1 表达和 Notch-1 核易位。Jag-1 对 Notch-1 信号的激活增加了 Ki67、PCNA 和修复过程，但降低了细胞内 IL-33 和 p21 的表达，而不影响细胞增殖。DAPT 抵消了 Notch-1 激活对 PCNA 和 IL-33 的影响。CSE 增加 Ki67、PCNA、p21 和 IL-33 的表达，但减少细胞增殖和修复过程。总之，香烟烟雾暴露，