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支架蛋白IQGAP1参与气道上皮细胞损伤修复过程

汪永平, 王芳, 王满香, 朱敏, 马燕, 吴人亮

华中科技大学同济医学院同济医院病理研究所

摘要

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。该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#beta#--catenin核转位,从而活化Tcf/Lef信号。此外,刮伤还影响IQGAP1与#beta#--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。

关键词： IQGAP1; 损伤修复; 气道上皮细胞

IQ domain GTPase--activating protein 1 mediates the process of injury and repair in bronchial epithelial cells

Wang Yongping, Wang Fang, Wang Manxiang, Zhu Min, Ma Yan, Wu Renliang

Institute of Pathology,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Key Laboratory of Pulmonary Disease of Ministry of Health of China.Wuhan 430030,Hubei

Abstract

The process of injury and repair in airway epithelium involves 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 identified in lung epithelial cells. In this study, we utilized a widely used model in vitro by scratching bronchial epithelial cells (BECs) and investigated the function of IQGAP1. The results shower that IQGAP1 was abundant in BECs of several species. It was colocalized with tubulin cytoskeleton, but was destroyed by nocodazole, a microtubule disassembled reagent. IQGAP1 mRNA and protein expressions increased at 6-9 h after scratching. In addition, enforced overexpression of IQGAP1 translocated #beta#-catenin from the cytoplasm into the nucleus and activated the Tcf/Lef signal. Scratching altered the associations of IQGAP1 with #beta#-catenin, adenomatous polyposis coli (APC) and cytoplasmic linker protein-170 (CLIP-170). Depletion of IQGAP1 by small interference RNA (siRNA) blocked the wound closure. It is conclude that IQGAP1 signal is involved in the wound closure of BECs induced by scratching.

Key words: IQ domain GTPase-activating protein 1;injury and repair;bronchial epithelial cells

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引用本文：

汪永平, 王芳, 王满香, 朱敏, 马燕, 吴人亮. 支架蛋白IQGAP1参与气道上皮细胞损伤修复过程[J]. 生理学报 2008; 60 (3): 409-418.

Wang Yongping, Wang Fang, Wang Manxiang, Zhu Min, Ma Yan, Wu Renliang. IQ domain GTPase--activating protein 1 mediates the process of injury and repair in bronchial epithelial cells. Acta Physiol Sin 2008; 60 (3): 409-418 (in Chinese with English abstract).