Prolonged parenchymal cell death leads to activation of fibrogenic cells, extracellular matrix accumulation, and eventually liver fibrosis. Increasing evidence shows that exosomes (Exos) secreted by adipose-derived mesenchymal stem cells (ADSCs) can be used to deliver circular RNAs (circRNAs) to treat liver fibrosis. To explore the uses of circRNA, circRNA expression profiles of hepatic tissue from normal and CCl₄-induced mice were analyzed using high-throughput circRNA microarrays. The result showed that mmu_circ_0000623 expression was downregulated in CCl₄-induced mice. Bioinformatics analysis and luciferin reporter experiments showed that mmu_circ_0000623 interacted with and regulated miR-125/ATG4D. In vitro and in vivo experiments showed that Exos from ADSCs, especially from mmu_circ_0000623-modified ADSCs, significantly suppressed CCl₄-induced liver fibrosis by promoting autophagy activation. Autophagy inhibitor treatment significantly reversed the treatment effects of Exos. Proteins involved in autophagy and autophagy plaques positive for ATG4D expression were regulated by mmu_circ_0000623/miR-125. Our study found that Exos derived from mmu_circ_0000623-modified ADSCs prevented liver fibrosis via activating autophagy.

长时间的实质细胞死亡导致纤维化细胞活化、细胞外基质积累，并最终导致肝纤维化。越来越多的证据表明，脂肪源性间充质干细胞（ADSC）分泌的外泌体（Exos）可用于递送环状RNA（circRNA）来治疗肝纤维化。为了探索 circRNA 的用途，使用高通量 circRNA 微阵列分析了正常小鼠和 CCl _{4诱导小鼠肝组织的 circRNA 表达谱。}结果显示，CCl ₄诱导的小鼠中mmu_circ_0000623表达下调。生物信息学分析和荧光素报告基因实验表明mmu_circ_0000623与miR-125/ATG4D相互作用并对其进行调节。体外和体内实验表明，来自ADSC，特别是来自mmu_circ_0000623修饰的ADSC的Exos，通过促进自噬激活显着抑制CCl _{4诱导的肝纤维化。}自噬抑制剂治疗显着逆转了 Exos 的治疗效果。参与自噬的蛋白质和 ATG4D 表达呈阳性的自噬斑块受 mmu_circ_0000623/miR-125 调节。我们的研究发现，源自 mmu_circ_0000623 修饰的 ADSC 的 Exos 通过激活自噬来预防肝纤维化。