真皮鞘细胞参与皮肤创伤修复的作用机制：基于Cre/loxP重组系统的示踪研究

真皮成纤维细胞是参与皮肤创伤修复的主要功能细胞，而作为其特化亚群之一的真皮鞘细胞最近被证明也参与了该过程。角蛋白是参与皮肤创伤修复的重要蛋白，一般认为只在上皮细胞表达。我们前期研究发现，真皮鞘细胞具有类似真皮成纤维细胞的生物学行为，且多种角蛋白在真皮鞘细胞中特异表达。据此，本研究拟利用Cre/loxP系统建立真皮鞘细胞特异性表达eGFP小鼠模型，深入研究全层皮肤创伤修复过程中真皮鞘细胞的谱系示踪、分化机制及角蛋白K5、K17的时空表达变化；探讨创伤修复过程中真皮鞘细胞经细胞衰老途径防止过度纤维化的信号通路机制；利用慢病毒转染和RNA干扰技术阐明K5、K17过表达或抑制表达对真皮鞘细胞增殖、迁移、衰老、凋亡、细胞周期，以及对皮肤创伤愈合和纤维化等生物学行为的效应。本研究将揭示皮肤创伤修复期间真皮鞘细胞的作用机制及与真皮成纤维细胞作用的异同，为皮肤创伤、烧伤和疾病治疗新技术的研发提供理论依据。

Dermal fibroblasts are the main functioning cells in skin wound healing, while dermal sheath cells, as one of their specialized subsets, have recently been proved to be also involved in this process. Keratins are important proteins involved in skin wound healing, and they are generally believed only expressed in epithelial cells. In our previous studies, we found that dermal sheath cells had biological behavior similar to dermal fibroblasts, and expressed a variety of keratins specifically. Based on this, our study is going to establish mouse models with eGFP specially expressed in dermal sheath cells by using the Cre-loxP system, for study on the lineage tracing, differentiation mechanism and K5/K17 expression changes in space and time of dermal sheath cells during full-thickness skin wound healing process; To explore the signal mechanism of dermal sheath cells preventing excessive fibrosis through cell senescence in wound repair; To elucidate the biological behavior effects of overexpression or inhibition of K5 or K17 of dermal sheath cells on cell proliferation, migration, senescence, apoptosis and cycling, as well as skin wound healing and fibrosis, by using lentivirus transfection and RNA interference techniques . This study will reveal the functional mechanism of dermal sheath cells during wound healing and the similarities and differences between dermal sheath cells and dermal fibroblasts, and provide a theoretical basis for exploiting new therapies in field of skin trauma, burns and diseases.