CD9/E-cadherin调节表皮细胞分化的作用及机制研究

创面再上皮化是创面愈合的关键环节，表皮细胞分化调控贯穿于创面再上皮化过程，主要表现为早期新生表皮维持低分化状态高运动性而后期则需重塑表皮分化梯度。我们前期研究在明确“创面愈合早期新生表皮CD9下调促进细胞迁移，后期又恢复正常水平”的基础上发现CD9可调控表皮细胞分化，但机制尚不清楚。E-cadherin介导的细胞间粘附连接可促进表皮细胞分化，结合相关进展，我们提出“CD9同E-cadherin相互作用，使E-cadherin向表皮细胞膜上募集从而促进表皮细胞分化”的科学假设。研究拟首先从动物和细胞水平进一步明确CD9对表皮细胞分化的影响；继而检测CD9同E-cadherin相互作用及其调节表皮细胞分化的关键结构域；最后明确E-cadherin在CD9调节的表皮细胞分化中的作用。研究对深入揭示CD9调节表皮细胞分化的作用机理，深化对创面愈合发生机制的认识，有重要的理论意义和潜在的临床价值。

Wound reepithelialization is a critical point in the process of wound healing. The regulation of keratinocyte differentiation is existing throughout the reepithelialization. In the early stage of wound healing, the new epidermis is in the low differentiation status and high motility, while in the late stage the new epidermis will differentiate to promote epidermal differentiation gradient formation. Our previous research revealed that CD9 expression in the migrating epidermis is downregulated following wounding and then increases, reaching levels comparable to that observed in normal skin epidermis when reepithelialization is complete. Mealwile, we also identified that CD9 regulates keratinocyte differentiation, but the mechanism remains unclear. E-cadherin mediated cell-cell junction plays an important role in keratinocyte differentiation. We hypothesize here that "CD9 interacts with E-cadherin interaction and recruits E-cadherin to the plasma membrane so as to promote keratinocyte terminal differentiation". To test it, we would set up experiments to further confirm the effect of CD9 on keratinocyte differentiation in both cultured keratinocyte and mice epidermis; and then investigate the expression, location and direct interaction of CD9 with E-cadherin; and reveal the structure domain in CD9 that mediates the interaction with E-cadherin in the regulation of keratinocyte differentiation; finally, to test the role of E-cadherin in the regulation of CD9-mediated keratinocyte differentiation. These studies, taken together, would enable us a better understanding of how CD9 participates in wound reepithelialization and be involved in physiological wound healing, which has important theoretical significance and potential application value.