IQGAP1 promotes cell proliferation and is involved in a phosphorylation-dependent manner in wound closure of bronchial epithelial cells.
The re-epithelialization process of the airway involves spreading and migration followed by cell proliferation. Scaffold IQ domain GTPase-activating protein (IQGAP1), an effector of Rho GTPases, is a key component in a series of cell processes, although its exact mechanism in injury and repair of the airway is still unclear. In this study, we utilized a widely used model in vitro by scratching bronchial epithelial cells (BECs). At different time points after scratching, the amounts of IQGAP1 in mRNA and protein were greater than that in the control. PKCepsilon-mediated phosphorylation of IQGAP1 was involved in the process of injury and repair. The overexpression of PKCepsilon or treatment with phorbol-12-myristate-13-acetate (the PKC activator) promoted wound closure. On the contrary, the group treated with GF109203X (the PKC inhibitor) had the opposite effect. Scratching or overexpression of IQGAP1 induced increasing amounts of total beta-catenin and the transposition of beta-catenin from the cytoplasm into the nucleus. These results activated the T cell factor/lymphoid enhanced factor and induced expression levels of its target genes of c-myc and cyclin D1. The reduction of IQGAP1 by the transfection of small interference RNA of IQGAP1 attenuated these effects and directly impaired the scratching-induced wound closure. Taken together, our results suggest that IQGAP1 promotes cell proliferation and phosphorylation of IQGAP1 is involved in the process of wound closure in BECs.
Wang
Yongping
Y
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, PR China.
Wang
Manxiang
M
Wang
Fang
F
Zhu
Min
M
Ma
Yan
Y
Wang
Xi
X
Wu
Renliang
R
D001980:Bronchi / Q000201:enzymology / Q000473:pathology*; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000378:metabolism; D004847:Epithelial Cells / Q000201:enzymology / Q000473:pathology*; D005786:Gene Expression Regulation; D006801:Humans; D010766:Phosphorylation; D051744:Protein Kinase C-epsilon / Q000378:metabolism; D021381:Protein Transport; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051820:TCF Transcription Factors / Q000378:metabolism; D014945:Wound Healing; D051176:beta Catenin / Q000378:metabolism; D020703:ras GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism*
C101203:IQ motif containing GTPase activating protein 1; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D051820:TCF Transcription Factors; D051176:beta Catenin; D020703:ras GTPase-Activating Proteins; D019938:Cyclin D1; D051744:Protein Kinase C-epsilon