支架蛋白IQGAP1参与气道上皮细胞损伤修复过程(英文)

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气道上皮损伤修复过程包括细胞延伸、迁移和增殖。IQGAP1(IQ domain GTPase-activating protein1)是一个在许多细胞生命活动中非常有意义的蛋白,但其在肺上皮细胞中的作用尚未阐述清楚。本文采用目前广泛应用的刮伤气道上皮细胞的体外模型来研究IQGAP1的功能。结果显示,IQGAP1在小鼠、大鼠、猪和人气道上皮细胞中有丰富表达。它与微管骨架共定位,可被微管解聚剂nocodazole破坏。刮伤6~9h后,IQGAP1mRNA及蛋白表达上调。过表达外源性IQGAP1导致β-catenin核转位,从而活化Tcf/Lef信号。此外,刮伤还影响IQGAP1与β-catenin、结肠腺瘤病(adenomatous polyposis coli,APC)蛋白及细胞质连接蛋白-170(cytoplasmic linker protein-170,CLIP-170)之间的相互作用。通过小干扰RNA(small interferenceRNA,siRNA)沉默IQGAP1表达则明显延迟损伤愈合。结果提示,IQGAP1信号参与气道上皮细胞损伤修复过程。 Airway epithelium injury repair process includes cell extension, migration and proliferation. IQGAP1 (IQ domain-activating protein1) is a protein that is of great interest in many cell-life activities, but its role in lung epithelial cells has not yet been elucidated. In this paper, the currently widely used in vitro model of airway epithelial cells was used to study the function of IQGAP1. The results showed that IQGAP1 was abundantly expressed in mouse, rat, pig and human airway epithelial cells. It co-localizes with the microtubule framework and can be destroyed by microtubule depolymerisation nocodazole. Scratch 6 ~ 9h, IQGAP1 mRNA and protein expression. Overexpression of exogenous IQGAP1 leads to nuclear translocation of β-catenin, thereby activating Tcf / Lef signaling. In addition, scratching also affects the interaction between IQGAP1 and β-catenin, adenomatous polyposis coli (APC) protein and cytoplasmic linker protein-170 (CLIP-170). Silencing IQGAP1 expression by small interference RNA (siRNA) significantly delayed wound healing. The results suggest that IQGAP1 signal involved in airway epithelial cell injury repair process.
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