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 

机构地区：[1]Department of Plastic Surgery,State Key Laboratory of Trauma,Burns and Combined Injury,Southwest Hospital,Third Military Medical University(Army Medical University),29 Gaotan Yan Street,Shapingba,400038 Chongqing,China

出　　处：《Burns & Trauma》2023年第1期361-374,共14页烧伤与创伤（英文）

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).

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 healing.Although 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 unclear.This study aims to determine how the leader cells are polarized and coordinated during EF-guided collective migration of epidermal cell sheets.Methods:Collective migration of the human epidermal monolayer(human immortalized ker-atinocytes HaCaT)under EFs was observed via time-lapse microscopy.The 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 manipulation.Blocking,rescue and co-culture experiments were conducted to explore the downstream signalling of CD9.Results: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 EFs.By confocal microscopy,we found that CD9 was colocalized with F-actin on the cell surface and was particularly downregulated in leader cells by EFs.Interestingly,genetic overexpression of CD9 abolished EF-induced F-actin polarization in leader cells as well as collective migration in the epidermal monolayer.Mechanistically,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)signalling.The abolished polarization of leader cells due to CD9 overex-pression could be restored in a co-culture monolayer where normal cells and CD9-overexpressing cells were mixed;how

关 键 词：CD9 Electric fields Collective migration Wound healing F-actin polarization leader cells 

分 类 号：R644[医药卫生—外科学]