中文摘要
皮肤大面积创伤造成的疤痕形成,给患者带来极大的心理和生理痛苦。如何减少疤痕形成,促进功能性皮肤再生,是组织再生领域的焦点问题之一,而寻找调节毛囊发生和皮肤纤维化的信号分子则是解决以上问题的关键!我们前期研究发现,在毛囊真皮鞘细胞中激活β-catenin能够先后诱导异位毛囊新生和真皮纤维化发生,提示Wnt信号可能是决定间充质细胞往两个不同方向发展的关键信号通路。本研究利用流式细胞术分选真皮鞘细胞进行microarray分析,对候选基因进行体外表达调控和体内表达谱验证,分析诱导毛囊发生的“第一真皮信号”;利用细胞追踪技术对毛囊真皮鞘细胞进行跟踪,分析纤维化发生的细胞行为;利用皮肤创伤试验研究Wnt信号对毛囊再生与纤维化形成的协调作用。本研究将有助于解析毛囊新生和皮肤纤维化发生机制,并通过调控Wnt信号协调毛囊再生和纤维化发生,对促进创伤后功能性皮肤再生有着重要的理论意义和临床应用价值。
英文摘要
Most patients would be psychologically and physiologically suffered from the large-area scar resulted from the serious skin wounding. How to reduce the scar formation and how to improve the formation of functional skin with hair follicle, sebaceous gland, and sweat gland, is a crucial question in the tissue regeneration field. Furthermore, it is critical to find some key signals or molecules which can regulate hair follicle initiation and skin fibrosis formation. In our previous study, we found that β-catenin activation in hair follicle dermal sheath is able to induce ectopic hair outgrowth and skin fibrosis, indicating that Wnt signal is a possible key pathway to determine the dermal mesenchymal cells develop into hair follicle or fibrosis. In current study, first, to understand “the first dermal signal” which induces placode formation and hair follicle initiation, we will sort dermal sheath cell by using flow cytometry and do microarray analysis, and then analyze the candidates by in vitro reporter assay and in vivo gene expression pattern detection. Second, we would analyze the dermal sheath cell behavior during skin fibrosis formation by using cell lineage tracing experiment. Finally, the regulation of different Wnt signal level on hair follicle initiation and dermal fibrosis formation will be studied through skin wounding. These studies would help to discover the mechanism of hair follicle inducing and fibrosis formation. Moreover, hair follicle regeneration and fibrosis formation could be regulated through controlling the level of Wnt signal. Taken together, our study will provide some novel theoretical and clinical insights for wound healing and functional skin regeneration.
