LncRNA-NR002819/Pygo2调控皮肤成纤维细胞衰老的作用及机制研究

How to postpone skin aging is one of the most significant clinical problems that perplex plastic and aesthetic surgeons. However, there is so far no effective long-term therapeutic treatment, since the mechanisms of cell aging is still unclear. Recent research demonstrated that LncRNA was the key factor in the regulation of cell aging. We found in our previous research that LncRNA-NR002819 was high expressed in old people skin tissues. Blast testing showed that partial gene region of Pygo2 could be the combine locus of LncRNA-NR002819. As former study confirmed, Pygo2 specifically activates down-stream signal pathway and regulates skin cell aging. Meanwhile, our preliminary experiments verified that LncRNA-NR002819/Pygo2 influences age-related signal, and regulates skin fibroblast aging. In the present project, cytological experiment, animal model, trans-genetic and gene-sequencing technology will be applied, in order to reveal the mechanisms of LncRNA-NR002819 regulating Pygo2 gene expression, and identify their possible role in skin fibroblast aging.

皮肤衰老是整形美容医生需要面对的重要临床问题，但缺乏有效的长期干预措施，其主要原因是对细胞衰老的机制尚不完全清楚。最新研究表明LncRNA可能是细胞衰老过程中重要的调控因子。申请人前期研究发现LncRNA-NR002819在老年人群皮肤组织中高表达。通过数据库比对，申请人发现LncRNA-NR002819可能通过与Pygo2基因局部片段结合进而发挥作用，而Pygo2被认为可特异性激活下游信号路通调节皮肤细胞衰老。因此，申请人提出，并通过预实验初步证实LncRNA-NR002819与Pygo2可能通过相互作用进而影响下游衰老相关信号，参与皮肤成纤维细胞衰老的调控。因此本项目拟通过细胞学实验、动物模型实验，运用转基因技术、基因测序等手段，揭示LncRNA-NR002819调控Pygo2基因表达的分子机制，初步阐明LncRNA-NR002819/Pygo2参与皮肤成纤维细胞衰老的作用机制。

人体衰老是事关国计民生的重大课题，皮肤衰老是整形外科学学科领域中的重要科学问题，但缺乏有效的干预措施。在项目资助下，主要完成了细胞学实验、动物模型实验，运用转基因技术、基因测序等手段，初步阐明了LncRNA-NR002819通过Pygo2以及TIMP1-GPI干预皮肤衰老的分子机制，基因芯片数据显示长链非编码RNA-NR002819与皮肤衰老相关，Western数据显示其调节衰老的机制主要通过Pygo2蛋白、TIMP蛋白及其他细胞膜结合蛋白。然而，TIMP的调节作用存在抑制或者促进衰老的多向性。细胞学实验显示细胞膜结合锚定蛋白GPI的TIMP1能够抑制细胞增殖，促进凋亡。因此我们认为，LncRNA-NR002819通过TIMP1调节皮肤衰老的过程，能够被结合了锚定蛋白GPI的TIMP1所改变，从而达到抗衰老的效果。本项目结果揭示了LncRNA-NR002819通过过Pygo2及TIMP1-GPI干预皮肤衰老的分子机制，初步阐明TIMP1和其他膜结合蛋白及其下游分子参与皮肤衰老的作用机制，为临床抗衰老医学实践提供借鉴。