心肌纤维化是多种心脏疾病的共同病理改变，可导致心力衰竭和心律失常，但其确切分子机制仍有待阐明。我们前期发现非编码RNA miR-101/133/590/21是心肌纤维化的调控分子。长链非编码RNA（lncRNA）是新近引起广泛关注的一类参与重大疾病调节的分子，其与心肌纤维化的关系仍未知。我们发现压力超负荷及缺血纤维化小鼠心肌组织的lncRNA表达谱发生改变，并筛选出与心肌纤维化通路关系密切的67个lncRNAs，且在血管紧张素II刺激的成纤维细胞模型得到验证。两种模型发现9个共性变化的lncRNAs，选择4个作为研究对象。另外，发现MIAT具有抗纤维化作用并与miR-24表达调节相关。因此，我们假设：以上5个lncRNA对心肌纤维化具有调节作用，其机制与调节miRNA及相关纤维化通路有关。我们将应用RIP、蛋白质组学、模式动物等方法验证上述假设，阐明lncRNA调控心肌纤维化的作用与机制。

Cardiac fibrosis is the common pathological changes occurred in various cardiac diseases, which can lead to heart failure and arrhythmia. However, the molecular mechanisms remain to be explored. Previously, we found that miR-101/133/590/21 are the critical regulators of cardiac fibrosis. Lately, lncRNAs (Long noncoding RNAs) draw the attention of researchers and are proved to be a new class of regulators in various diseases. Currently, the biological role of lncRNAs in cardiac fibrosis is largely unknown. In our preliminary work we found that the lncRNA expression profiles were significantly altered in fibrotic hearts induced by pressure overload and cardiac infarction, and 67 lncRNAs were predicted to interact with fibrosis-related signaling pathways. Among them, 9 lncRNAs showed expression changes in the same direction in both models. We selected 4 of them for further study. Moreover, we found that MIAT (myocardial infarction associated transcript) participated in the regulation of cardiac fibroblast proliferation and collagen production, which is correlated with the regulation of miR-24 expression. Therefore, we hypothesized that the above 5 lncRNAs are key molecules in regulating cardiac fibrosis, and the mechanisms involve the manipulation of miRNA expression and fibrosis related signaling pathways. In the current project, we will employ RIP, protein mass spectrometry, and genetic manipulated mice model to test the hypothesis at both in vitro and in vivo level in order to confirm the effects of lncRNA on cardiac fibrosis and underlying mechanism.