LncRNA-H19调控APPL1/AMPKα1促进MRTF-A核移位介导骨髓来源纤维母细胞在肾脏IRI后期纤维化中的作用

纤维化是慢性肾脏疾病的最终共同表现。大量研究表明lncRNA很可能成为潜在的肾脏纤维化的生物标志物和新的治疗靶点。基于前期研究基础，我们采用二代测序技术结合生物信息学分析确定lncRNA-H19作为进一步研究的作用靶点。本课题组前期研究已证实APPL1在肾脏IRI后期纤维化形成的过程中发挥重要作用，通过预实验和生物信息学结果分析，我们推测lncRNA-H19在IRI后期肾脏纤维化过程中的作用可能与APPL1/ AMPKα1和MRTF-A核移位有关。因此，本课题建立小鼠肾脏IRI后纤维化动物模型，选用基因敲除小鼠作为研究工具，借助骨髓移植的实验手段，研究lncRNA-H19调控APPL1/ AMPKα1促进MRTF-A核移位介导骨髓来源纤维母细胞在肾脏IRI后期纤维化中的作用。

Fibrosis is the ultimate common manifestation of chronic kidney disease. A large number of studies have shown that lncRNA is likely to become a potential biomarker of renal fibrosis and a new therapeutic target. Based on the previous research, we used second-generation sequencing technology combined with bioinformatics analysis to determine lncRNA-H19 as a target for further research. The previous studies of our group have confirmed that APPL1 plays an important role in the formation of renal fibrosis in the late stage of IRI. Through the analysis of the results of pre experiment and bioinformatics, we speculated that the role of lncRNA-H19 in the process of renal fibrosis in the late stage of IRI may be related to the nuclear translocation of APPL1 / AMPK α 1 and MRTF-A.Therefore, we established the animal model of renal fibrosis after IRI in mice. We used knockout mice as the research tool to study the role of lncRNA-H19 in the regulation of APPL1 / AMPK α 1 to promote MRTF-A nuclear translocation and mediate the role of bone marrow-derived fibroblasts in renal fibrosis after IRI.