CD9 negatively regulates collective electrotaxis of the epidermal monolayer by controlling and coordinating the polarization of leader cells

作     者：Xiaoqiang Liu Jinrui Yang Meng Kong Min Jiang Luojia Liu Jinghong Zhang Ying Chen Xu Chen Ze Zhang Chao Wu Xupin Jiang Jie Liu Jiaping Zhang 

作者机构：Department of Plastic SurgeryState Key Laboratory of TraumaBurns and Combined InjurySouthwest HospitalThird Military Medical University(Army Medical University)29 Gaotan Yan StreetShapingba400038 ChongqingChina 

出 版 物：《Burns & Trauma》 (烧伤与创伤（英文）)

年 卷 期：2023年第11卷第1期

页      面：361-374页

核心收录：

学科分类：1002[医学-临床医学] 100210[医学-外科学(含：普外、骨外、泌尿外、胸心外、神外、整形、烧伤、野战外)] 10[医学] 

基　　金：supported by the National Natural Science Foundation of China(NSFCNo.82272285,NSFC No.82002048 and NSFC No.82072172) the Scientific Research Project of Chongqing(CSTB2022BSXM-JCX0010) 

主　　题：CD9 Electric fields Collective migration Wound healing F-actin polarization leader cells 

摘      要：Background:Endogenous electric fields(EFs)play an essential role in guiding the coordinated collective migration of epidermal cells to the wound centre during wound *** polarization of leadercells is essential for collective migration,the signal mechanisms responsible for the EF-induced polarization of leader cells under electrotactic collective migration remain *** study aims to determine how the leader cells are polarized and coordinated during EF-guided collective migration of epidermal cell ***:Collective migration of the human epidermal monolayer(human immortalized ker-atinocytes HaCaT)under EFs was observed via time-lapse *** involvement of tetraspanin-29(CD9)in EF-induced fibrous actin(F-actin)polarization of leader cells as well as electrotactic migration of the epidermal monolayer was evaluated by genetic ***,rescue and co-culture experiments were conducted to explore the downstream signalling of ***:EFs guided the coordinated collective migration of the epithelial monolayer to the anode,with dynamic formation of pseudopodia in leader cells at the front edge of the monolayer along the direction of migration.F-actin polarization,as expected,played an essential role in pseudopod formation in leader cells under *** confocal microscopy,we found that CD9 was colocalized with F-actin on the cell surface and was particularly downregulated in leader cells by ***,genetic overexpression of CD9 abolished EF-induced F-actin polarization in leader cells as well as collective migration in the epidermal ***,CD9 determined the polarization of F-actin in leader cells by downregulating a disintegrin and metalloprotease 17/heparin-binding epidermal growth factor-like growth factor/epidermal growth factor receptor(ADAM17/HB-EGF/EGFR)*** abolished polarization of leader cells due to CD9 overex-pression could be restored in a co-culture monolayer where normal c