Cardiovascular disease (CVD) is the leading cause of mortality worldwide. Cardiac fibrosis is the scarring process occurs commonly with CVDs impairing the function and structure of heart. Herein, we investigated the role of in the pathogenesis of cardiac fibrosis. A rat myocardial infarction (MI) model was constructed to evaluate the role of . Expression of in MI was determined, and si- was applied to verify its profibrotic effects. With an in vitro model, cardiac fibroblasts were stimulated by transforming growth factor beta 1 (TGFβ1). Immunofluorescent staining was employed to assess the fibrosis-related markers, as well as autophagy activity. CCK-8 and transwell assays were performed to determine cell proliferation and migration. Luciferase reporter assay and RNA pull-down were subjected to verify the interaction of . The enrichment of FoxO3 on the promoter region of ATG7 was detected using CHIP assay. Elevated was found in rat MI heart tissue, of which knockdown attenuated cardiac fibrosis after MI. In an in vitro model exposing with TGFβ1, increasing cell proliferation and migration were observed, whereas these effects were abolished by knockdown, as well as autophagy activity. was identified as a target to be involved in -mediated cardiac fibrosis after MI. negatively regulated FoxO3, thus causing the inhibition of ATG7 transcription. The regulatory network of //FoxO3/ATG7 in cardiac fibrosis was further determined in vivo. exhibited profibrotic effects during autophagy-mediated cardiac fibrosis via /FoxO3/ATG7 axis, which may serve as potential biomarkers for cardiac fibrosis therapeutics.

中文翻译：

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在心肌梗死大鼠模型中，circPAN3 通过 FoxO3/ATG7 激活的自噬作用海绵 miR-221 发挥促纤维化作用

心血管疾病（CVD）是全世界死亡的主要原因。心脏纤维化是心血管疾病常见的疤痕形成过程，损害心脏的功能和结构。在此，我们研究了在心脏纤维化发病机制中的作用。构建大鼠心肌梗死（MI）模型来评估 的作用。测定MI中的表达，并应用si-验证其促纤维化作用。在体外模型中，转化生长因子β1（TGFβ1）刺激心脏成纤维细胞。采用免疫荧光染色来评估纤维化相关标记物以及自噬活性。进行 CCK-8 和 Transwell 测定以确定细胞增殖和迁移。荧光素酶报告基因测定和 RNA Pull-down 被用来验证 的相互作用。使用CHIP 测定检测ATG7 启动子区域上FoxO3 的富集。在大鼠 MI 心脏组织中发现其升高，其中的敲低可减轻 MI 后的心脏纤维化。在暴露于 TGFβ1 的体外模型中，观察到细胞增殖和迁移增加，而这些效应被敲低以及自噬活性所消除。被确定为参与 MI 后介导的心脏纤维化的靶标。负调节 FoxO3，从而抑制 ATG7 转录。 //FoxO3/ATG7在心脏纤维化中的调节网络在体内得到进一步确定。通过 /FoxO3/ATG7 轴在自噬介导的心脏纤维化过程中表现出促纤维化作用，这可能作为心脏纤维化治疗的潜在生物标志物。