CCL18与MAPT结合通过抑制自噬和触发细胞衰老促进慢性阻塞性肺疾病
CCL18 binding to MAPT promotes chronic obstructive pulmonary disease by inhibiting autophagy and triggering cell senescence.
摘要(中文译文)
趋化因子CCL18在慢性阻塞性肺疾病（COPD）中表达上调，但其在疾病进展中的作用仍不清楚。本研究旨在确定CCL18是否通过MAPT介导的自噬和细胞衰老调控参与COPD的发病机制。采用香烟烟雾（CS）和香烟烟雾提取物（CSE）建立COPD动物和细胞模型。使用RT-qPCR、Western blot、SA-β-Gal染色、流式细胞术、ELISA和苏木精-伊红（H&E）染色进行分析。结果显示，CCL18在临床COPD样本和实验模型中表达升高。敲低CCL18表达可抑制细胞衰老标志物VEGF和MMP1的mRNA表达以及p27、p16和p21蛋白的表达，同时促进Lamin B1、LC3Ⅱ/Ⅰ和Beclin1蛋白的表达。它还可降低IL-6、IL-1β、TNF-α和ROS水平，减轻小鼠肺部病理损伤，并延缓COPD进展。机制研究揭示，CCL18通过上调MAPT表达抑制自噬，从而促进细胞衰老并加速COPD的发展。这些发现表明，靶向下调CCL18表达可能为COPD提供一种新的治疗策略。
Abstract
The expression of the chemokine CCL18 is upregulated in chronic obstructive pulmonary disease (COPD), yet its role in disease progression remains unclear. This study aimed to determine whether CCL18 participates in the pathogenesis of COPD through MAPT-mediated regulation of autophagy and cellular senescence. COPD animal and cell models were established using cigarette smoke (CS) and cigarette smoke extract (CSE). Analyses were conducted using RT-qPCR, Western blot, SA-β-Gal staining, flow cytometry, ELISA, and H&E staining. The results revealed that CCL18 expression was elevated in clinical COPD samples and experimental models. Knockdown of CCL18 expression suppressed the mRNA expression of the cellular senescence markers VEGF and MMP1, as well as the p27, p16, and p21 proteins, while it promoted the expression of Lamin B1, LC3Ⅱ/Ⅰ, and Beclin1 proteins. It also reduced the levels of IL-6, IL-1β, TNF-α, and ROS; alleviated pathological lung injury in mice; and delayed COPD progression. Mechanistic studies revealed that CCL18 inhibits autophagy by upregulating MAPT expression, thereby promoting cellular senescence and accelerating the development of COPD. These findings suggest that targeted downregulation of CCL18 expression may offer a novel therapeutic strategy for COPD.
如何引用
AMA
Hongbo Chen, Lina Wang, Jie Liu, Yu Zhang. CCL18 binding to MAPT promotes chronic obstructive pulmonary disease by inhibiting autophagy and triggering cell senescence.. Tissue & cell. 2026; doi:10.1016/j.tice.2026.103415.
APA
Hongbo Chen, Lina Wang, Jie Liu, Yu Zhang (2026). CCL18 binding to MAPT promotes chronic obstructive pulmonary disease by inhibiting autophagy and triggering cell senescence.. Tissue & cell. https://doi.org/10.1016/j.tice.2026.103415
GB/T 7714
Hongbo Chen, Lina Wang, Jie Liu, Yu Zhang. CCL18 binding to MAPT promotes chronic obstructive pulmonary disease by inhibiting autophagy and triggering cell senescence.[J]. Tissue & cell, 2026 doi:10.1016/j.tice.2026.103415.
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