医学
肌动蛋白细胞骨架
PI3K/AKT/mTOR通路
蛋白激酶B
主动脉瘤
机制(生物学)
信号转导
药理学
细胞生物学
癌症研究
细胞骨架
动脉瘤
生物
细胞
生物化学
外科
哲学
认识论
作者
Zhaoran Chen,Jianhuang Wu,Wei Wang,Xiaonan Tang,Lei Zhou,Yanze Lv,Yuehong Zheng
摘要
Aortic aneurysm and dissection (AAD) is a life-threatening disease worldwide. Recently, fluoroquinolones have been reported to significantly increase the risk of AAD. This study aimed to investigate the potential functional mechanism and molecular targets of fluoroquinolones in relation to AAD by an integrated proteomic and network pharmacology strategy. A total of 1351 differentially expressed proteins were identified in human aortic vascular smooth muscle cells (VSMCs) after ciprofloxacin (CIP) stimulation. The functional analysis emphasized the important roles of metabolism, extracellular matrix homeostasis, mitochondrial damage, focal adhesion, and apoptosis in CIP-stimulated VSMCs. CIP targets were predicted with online databases and verified by molecular docking. Protein–protein interaction (PPI) analysis and module construction of the 34 potential CIP targets and 37 selected hub molecules after CIP stimulation identified four critical target proteins in the module: PARP1, RAC1, IGF1R and MKI67. Functional analysis of the PPI module showed that the MAPK signalling pathway, focal adhesion, apoptosis, regulation of actin cytoskeleton, and PI3K-Akt signalling pathway were significantly enriched. Our results will provide novel insights into the pathogenic mechanism of fluoroquinolones in aortic diseases.
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