miR-143调控线粒体自噬在难愈合性创面修复中的作用机制研究

Refractory wound not only brings great harm to patients’ daily life and quality of work, but also causes massive economic burdens to patient and whole society. Recent studies have found miR-143 was able to target the autophagy-related 2B, and autophagy of mitochondrial is closely related to mitochondrial function, which can promote survival rate of macrophage cells during wound healing. Researchers clarify the regulatory mechanisms of ischemia wound by mitophagy, may be the key issues in basic and clinical research currently refractory wound healing. Our pre-early experiments showed that the level of autophagy related protein LC3Ⅱin macrophages of chronic wounds was lower to which in healthy peripheral blood, blocking autophagy can raise ROS-mediated apoptosis of macrophage cells. To this end, the project intends to further study and clarify the miR-143 for mitochondrial autophagy regulation and mechanisms in macrophage cells; explore and reveal the role of HIF-1α in miR-143 regulated autophagy process in macrophage cells during refractory wound healing. In this way, we aim to look for the therapeutic targets from key molecular mechanisms about mitochondrial autophagy regulated by miR-143 in ischemia wound, and explore new prevention and treatment strategies to achieve theoretical innovative and breakthrough in applied research and in the clinical treatment of ischemia wound.

难愈合性创面具有病程长、对外观影响大以及并发症多等特点，不仅对患者的生活和工作质量造成了极大的危害，也为社会带来了重大的经济负担。最近研究发现，miR-143靶基因包含自噬相关基因ATG2B，而线粒体自噬与线粒体功能密切相关，能够促进创面中巨噬细胞在应激条件下存活。深入探索难愈合性创面的线粒体自噬调控机制，可能是目前难愈合性创面基础和临床研究的关键问题。我们的预初实验表明难愈合性创面内的巨噬细胞线粒体自噬发生标志蛋白LC3Ⅱ低于正常外周血中巨噬细胞，自噬的阻滞可导致由ROS介导的巨噬细胞凋亡。此外，我们还发现创面愈合中重要的调控因子HIF-1α同样也是miR-143的潜在靶基因。为此，本项目拟进一步研究揭示miR-143对难愈合性创面中巨噬细胞线粒体自噬的调控及机制；探讨miR-143如何通过HIF-1α调控难愈合性创面中巨噬细胞的线粒体自噬过程。藉此寻找治疗靶点，探索防治新策略。

难愈合性创面具有病程长、对外观影响大以及并发症多等特点，不仅对患者的生活和工作质量造成了极大的危害，也为社会带来了重大的经济负担。最近研究发现，miR-143靶基因包含自噬相关基因ATG2B，而线粒体自噬与线粒体功能密切相关，能够促进创面中巨噬细胞在应激条件下存活。深入探索难愈合性创面的线粒体自噬调控机制，可能是目前难愈合性创面基础和临床研究的关键问题。我们的预初实验表明难愈合性创面内的巨噬细胞线粒体自噬发生标志蛋白LC3Ⅱ低于正常外周血中巨噬细胞，自噬的阻滞可导致由ROS介导的巨噬细胞凋亡。此外，我们还发现创面愈合中重要的调控因子HIF-1α同样也是miR-143的潜在靶基因。为此，本项目拟进一步研究揭示miR-143对难愈合性创面中巨噬细胞线粒体自噬的调控及机制；探讨miR-143如何通过HIF-1α调控难愈合性创面中巨噬细胞的线粒体自噬过程。藉此寻找治疗靶点，探索防治新策略。