长链非编码RNA-ANHS抑制增生性瘢痕的作用机制研究

伤口愈合前微环境的缺氧状态可诱导HIF-1α表达促进伤口顺利愈合，但之后HIF-1α的异常持续高表达则会促进增生性瘢痕（HS）形成。本项目前期证实了在HS中高表达的miR-31-5p可通过靶向HIF-1α抑制因子（FIH）抑制其表达导致HIF-1α活性持续升高。在此基础上我们发现HIF-1α可诱导下游miR-31-5p表达升高，由此形成促进瘢痕增生的环形通路。而在非增生性瘢痕中miR-31-5p/FIH/HIF-1α通路没有持续激活，通过高通量测序和生物信息学分析等方法我们进一步研究发现lncRNA-ANHS在这一调控通路中起关键作用，拟阐明其作用机制并进行以lncRNA-ANHS为靶点的HS基因治疗方案的体内外验证，并尝试通过定量创伤患者血清中具有特殊稳定结构的lncRNA-ANHS降解残基这一无创筛查方法预测HS的发生风险，这将是国内外有关HS易感人群筛查的首次尝试。

The hypoxic state of the microenvironment of wound before healing can induce the expression of HIF-1α to promote wound healing. However, the abnormally high expression of HIF-1α can promote hypertrophic scar (HS) formation. In the early stage of our study, it was confirmed that the microRNA miR-31-5p, which is highly expressed in HS, inhibits expression of its direct target HIF-1α inhibitor (FIH), resulting in continuous increase of HIF-1α activity. On this basis, we found that HIF-1α can increase expression of miR-31-5p downstream, thereby forming a circular pathway to promote hypertrophic scar. However, in the non-hypertrophic scars, the miR-31-5p/FIH/HIF-1α pathway is not continuously activated. Further study with high-throughput sequencing and bioinformatics analysis illustrated that lncRNA-ANHS plays a key role in this process. We intend to elucidate its mechanism of function, and test HS gene therapy targeting lncRNA-ANHS in vitro and in vivo, and try to predict the risk of HS using a non-invasive screening method by quantifying lncRNA-ANHS residues with specific stable structure in serum of trauma patients, which is the first attempt to screen HS susceptible population at home and abroad.