Paxillin/HDAC6 regulates microtubule acetylation to promote directional migration of keratinocytes driven by electric fields

作者全名："Liu, Luojia; Liu, Xiaoqiang; Chen, Ying; Kong, Meng; Zhang, Jinghong; Jiang, Min; Zhou, Hongling; Yang, Jinrui; Chen, Xu; Zhang, Ze; Wu, Chao; Jiang, Xupin; Zhang, Jiaping"

作者地址："[Liu, Luojia; Liu, Xiaoqiang; Chen, Ying; Kong, Meng; Zhang, Jinghong; Jiang, Min; Zhou, Hongling; Yang, Jinrui; Chen, Xu; Zhang, Ze; Wu, Chao; Jiang, Xupin; Zhang, Jiaping] Third Mil Med Univ, Dept Plast Surg, State Key Lab Trauma Burns & Combined Injury, Southwest Hosp,Army Med Univ, Chongqing 400038, Peoples R China"

通信作者："Jiang, XP; Zhang, JP (通讯作者)，Third Mil Med Univ, Dept Plast Surg, State Key Lab Trauma Burns & Combined Injury, Southwest Hosp,Army Med Univ, Chongqing 400038, Peoples R China."

来源：BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:001113689600001

JCR分区：Q2

影响因子：5.1

年份：2024

卷号：1871

期号：2

开始页：　

结束页：　

文献类型：Article

关键词：Paxillin; Electric fields; Directional migration; Wound healing; Microtubule acetylation; Polarization

摘要："Endogenous electric fields (EFs) have been demonstrated to facilitate wound healing by directing the migration of epidermal cells. Despite the identification of numerous molecules and signaling pathways that are crucial for the directional migration of keratinocytes under EFs, the underlying molecular mechanisms remain undefined. Previous studies have indicated that microtubule (MT) acetylation is linked to cell migration, while Paxillin exerts a significant influence on cell motility. Therefore, we postulated that Paxillin could enhance EF-induced directional migration of keratinocytes by modulating MT acetylation. In the present study, we observed that EFs (200 mV/mm) induced migration of human immortalized epidermal cells (HaCaT) towards the anode, while upregulating Paxillin, downregulating HDAC6, and increasing the level of microtubule acetylation. Our findings suggested that Paxillin plays a pivotal role in inhibiting HDAC6-mediated microtubule acetylation during directional migration under EF regulation. Conversely, downregulation of Paxillin decreased microtubule acetylation and electrotaxis of epidermal cells by promoting HDAC6 expression, and this effect could be reversed by the addition of tubacin, an HDAC6-specific inhibitor. Furthermore, we observed that EFs also mediated the polarization of Paxillin and acetylated alpha-tubulin, which is critical for directional migration. In conclusion, our study revealed that MT acetylation in EF-guided keratinocyte migration is regulated by the Paxillin/HDAC6 signaling pathway, providing a novel theoretical foundation for the molecular mechanism of EF-guided directional migration of keratinocytes."

基金机构："National Natural Science Foundation of China (NSFC) [82072172, 82272285]"

基金资助正文："This research was generously supported by the National Natural Science Foundation of China (NSFC No. 82072172 and No. 82272285) . Our gratitude extends to all the individuals who actively participated in this study, whose invaluable contributions helped make this research possible. We would also like to express our appreciation to the members of the Plastic Surgery, State Key Laboratory of Trauma, Burns and Combined Injury, Southwest Hospital for their insightful discussions and valuable input."