CD9/Paxillin调节生物电场介导的表皮细胞方向性迁移的作用及机制研究

生物电场介导的表皮细胞方向性迁移是创面再上皮化的关键环节，而黏着斑组分Paxillin介导的细胞极化及骨架重构参与细胞方向性迁移的始动。我们前期研究发现CD9参与电场介导的表皮细胞方向性迁移调控，但机制尚不清楚。结合前期研究和文献，我们推测CD9通过同Paxillin相互作用影响HDAC6活性及微管乙酰化水平，是其调控电场介导的表皮细胞方向性迁移的重要机制。研究拟首先明确CD9在电场介导的表皮细胞方向性迁移中的作用；继而检测电场条件下CD9同Paxillin在方向性迁移表皮细胞中的表达定位、相互作用及其关键结构域，并阐明Paxillin在CD9调控的表皮细胞方向性迁移中的作用；最后明确HDAC6调节的微管乙酰化在电场下CD9/Paxillin介导的表皮细胞方向性迁移中的作用及机制。研究对深入揭示CD9调控表皮细胞方向性迁移作用机理，深化对创面愈合机制的认识有重要的理论意义和潜在的临床价值。

Physiological electric fields-induced directional keratinocyte migration is a critical point in the process of wound reepithelialization. Paxillin, a key component of the cellular adhesome, regulates cell polarization and cytoskeleton dynamic regulation, which plays an important role in the initiation of directional cell migration. Our previous research revealed that CD9 is involved in in electric fields-guided directional keratinocyte migration, but the mechanism remains unclear. Summarizing our previous results and literature, we propose that CD9 interacts with Paxillin to influence HDAC6 activity and the level of microtubules acetylation, thereby regulating electric fields-induced directional keratinocyte migration. To test it, we would set up experiments to further confirm the effect of CD9 on electric fields-induced directional keratinocyte migration; and then investigate the expression, location and direct interaction of CD9 with Paxillin, and reveal the structure domain in CD9 that mediates the interaction with Paxillin in directional migrating kerationcyte under electric fields; and elucidate the role of Paxillin in CD9-regulated directional keratinocyte migration; finally, to test the role and mechanism of HDAC6-regulated microtubule acetylation in CD9/Paxillin-mediated directional keratinocyte migration under electric fields. These studies, taken together, would enable us a better understanding of how CD9 participates in directional keratinocyte migration and is involved in physiological wound healing, which has important theoretical significance and potential clinical value.