缺氧诱导因子-1α/P311调控VEGF表达促进增生性瘢痕形成的分子机制研究

增生性瘢痕是继发于烧伤、创伤、手术外伤等皮肤损伤的常见临床难题，其发生机制尚未完全阐明，以至于临床防治效果有限。既往研究表明VEGF是促进增生性瘢痕形成的关键因子，但其上游调控机制仍不清楚。既往研究表明缺氧通过调控HIF-1α在调节VEGF的表达中发挥作用，我们进一步研究发现，在增生性瘢痕形成过程中，P311，一种促进增生性瘢痕形成的小分子，能够通过与HIF-1α相互作用调控VEGF的表达，并且HIF-α能够调控P311的表达。由此，我们提出“缺氧通过转录因子HIF-1α调控P311的表达，同时将P311招募至VEGF启动子区，二者协同促进VEGF转录，进而促进增生性瘢痕的发生”。本研究拟在建立缺氧模型的基础上，采用ChIP、reChIP、免疫共沉淀等技术，以“HIF-1α和P311”的相互关系为切入点，探讨增生性瘢痕发生的新机理，为寻找瘢痕防治的关键靶点提供新的思路和实验依据。

Hypertrophic scar is a highly prevalent condition secondary to skin injuries such as burns, trauma, and surgical trauma. As the underlying mechanisms are not fully understood，so that the clinical therapeutic effect was limited. VEGF was reported to be a key factor promoting the formation of hypertrophic scars, but its upstream regulatory mechanism is still unclear.Based on previous reports that hypoxia plays a role in regulating the expression of VEGF by mediating HIF-1α, Our further study found that in the process of hypertrophic scar formation, P311, a small molecule that promotes the formation of hypertrophic scar, can mediate the expression of VEGF by interacting with HIF-1α, and HIF-α can mediate the expression of P311.Therefore, we propose that " Hypoxia regulates the expression of VEGF through the transcription factor HIF-1α, HIF-1α regulates the expression of P311, and at the same time recruits P311 to the VEGF promoter region, HIF-1α and P311 synergistically promote VEGF transcription, and further cause the hypertrophic scars." Based on the hypoxic models, ChIP, reChIP, immunoprecipitation and other technologies, we focus on the relationship between "HIF-1α and P311" to explore the new mechanism of hypertrophic scars. We will provide new insights and experimental evidence for mechanisms of hypertrophic scar formation.