CAJ | 학술논문

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 protein 1)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,IQGAP1 mRNA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 interference RNA, 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.
기도상피손상수복과정포괄세포연신、천이화증식.IQGAP1 (IQ domain GTPase-activating protein 1)시일개재허다세포생명활동중비상유의의적단백,단기재폐상피세포중적작용상미천술청초.본문채용목전엄범응용적괄상기도상피세포적체외모형래연구IQGAP1적공능.결과현시,IQGAP1재소서、대서、저화인기도상피세포중유봉부표체.타여미관골가공정위,가피미관해취제nocodazole파배.괄상6～9h후,IQGAP1 mRNA급단백표체상조.과표체외원성IQGAP1도치β-catenin핵전위,종이활화Tcf/Lef신호.차외,괄상환영향IQGAP1여β-catenin、결장선류병(adenomatous polyposis coli, APC)단백급세포질련접단백-170 (cytoplasmic linker protein-170, CLIP-170)지간적상호작용.통과소간우RNA (small interference RNA, siRNA)침묵IQGAP1표체칙명현연지손상유합.결과제시,IQGAP1신호삼여기도상피세포손상수복과정.
The process of injury and repair in airway epithelium involves cell spreading and migration followed by cell proliferation. IQ domain GTPase-activating protein 1 (IQGAP1) acts in a series of cell processes, but has not been clarified in lung epithelial cells. In this study, a widely used model of injury and repair in vitro by scratching bronchial epithelial cells (BECs) was utilized to investigate the function of IQGAP1. The results showed that IQGAP1 was abundant in BECs of mouse, rat, pig and human. IQGAP1 was colocalized with tubulin cytoskeleton, but was destroyed by nocodazole, a microtubule disassembly reagent. IQGAP1 mRNA and protein expressions increased at 6-9h after scratching. In addition, overexpression of IQGAP1 translocated β-catenin from the cytoplasm into the nucleus and activated the Tcf/Lef signal. Scratching altered the associations of IQGAP1 with β-catenin, adenomatous polyposis coli (APC) and cytoplasmic linker protein-170 (CLIP-170). Silencing IQGAP1 expression by small interference RNA (siRNA) blocked the wound closure. It is concluded that IQGAP1 signal is involved in the wound closure of BECs induced by scratching.