适应性反应是药物性肝损伤中的特殊现象，它反映了恢复性组织修复在肝损伤转归中的关键作用，但其内在机制一直尚未明确。申请人前期研究发现川楝素引起的肝损伤具有适应性现象，且外泌体miR-106b可能通过靶向Vim在其中发挥促组织修复的关键作用。因此，本项目拟以川楝素肝损伤适应性反应为模式研究对象，采用荧光素酶报告系统、基因敲除等技术，首先确证Vim是miR-106b促组织修复的关键靶基因，明确miR-106b对Vim相关信号通路的调控作用，深入研究外泌体miR-106b的主要来源及其在细胞间的传递作用，阐明外泌体miR-106b介导促组织修复的确切分子事件及调控机制。并且，通过体内外及临床研究，辨析miR-106b与药物性肝损伤发生及预后的关系。这一创新研究将有助于深入认识药物性肝损伤适应性反应的内在机制，推动利用适应性反应治疗药物性肝损伤乃至其他肝脏疾病的研究进程。

Adaptive response is a special phenomenon in drug-induced liver injury (DILI), which reflects the key role of restorative tissue repair in the outcome of liver injury. However, the underlying mechanisms of adaptive response in DILI have not been clarified. The results from our previous study suggested that the adaptive response was existed in the mouse model of toosendanin-induced liver injury (TILI) and exosomal miR-106b targeting Vim may play an important role in this response by promoting tissue repair. Therefore, this project will focus on investigating the regulatory mechanism of exosomal miR-106b targeting Vim in the adaptive response of DILI, using TILI as an example. First, the techniques, including luciferase reporter system and gene knockout, will be used to verify Vim is the key target gene for miR-106b to promote tissue repair. The effects of miR-106b on the Vim related pathways will be also determined. Second, the major source of exosomal miR-106b and exosome-mediated transmission of miR-106b between the liver cells will be elucidated. Third, by the in vitro, in vivo, and clinical studies, the relationship between miR-106b and the occurrence and prognosis of DILI will be clarified. This project will not only help to understand the mechanism of adaptive response in DILI, but also will promote the use of adaptive response to prevent DILI and other liver diseases.