Downregulation of S100A4 Alleviates Cardiac Fibrosis via Wnt/β -Catenin Pathway in Mice
Downregulation of S100A4 Alleviates Cardiac Fibrosis via Wnt/β -Catenin Pathway in Mice
复制标题
S100A4 的下调通过 Wnt/β-连环蛋白途径减轻小鼠心脏纤维化
DOI：
10.1159/000489683
复制
发表时间：
2018-01-01
影响因子：
--
通讯作者：
Xu, Di
中科院分区：
文献类型：
--
作者：
Qian, LiJun;Hong, Jian;Xu, Di
背景/目的：心脏纤维化是心肌缺血性疾病进展过程中导致心脏重塑的病理变化，其治疗策略仍有待探索。 S100A4 是一种钙结合蛋白，参与纤维化疾病的机制尚不清楚。本研究旨在探讨S100A4在心脏纤维化中的作用。方法：分离培养新生C57BL/6小鼠心脏的心脏成纤维细胞。通过结扎左冠状动脉前降支（LAD）诱发心肌梗塞。假手术组不进行结扎。将5×105pfu/g腺病毒或5μM/g ICG-001心肌内注射到梗塞区或正常区边界的5个部位。我们利用Western blotting、定量RT-PCR、免疫荧光、免疫组织化学和Masson三色染色来探讨S100A4的功能。结果：我们发现体外和体内 S100A4 水平和心脏纤维化标志物以及 β-连环蛋白信号激活显着增加。此外，敲除S100A4可显着降低心脏纤维化和β-连环蛋白水平。此外，ICG-001抑制β-catenin信号通路后，S100A4的表达降低。结论：下调S100A4可通过Wnt/β-catenin通路减轻小鼠心脏纤维化。 S100A4可能是心脏纤维化的治疗靶点。
Background/Aims: Cardiac fibrosis is a pathological change leading to cardiac remodeling during the progression of myocardial ischemic diseases, and its therapeutic strategy remains to be explored. S100A4, a calcium-binding protein, participates in fibrotic diseases with an unclear mechanism. This study aimed to investigate the role of S100A4 in cardiac fibrosis. Methods: Cardiac fibroblasts from neonatal C57BL/6 mouse hearts were isolated and cultured. Myocardial infarction was induced by ligating the left anterior descending coronary artery (LAD). The ligation was not performed in the sham group. A volume of 5×105pfu/g adenovirus or 5 µM/g ICG-001 was intramyocardially injected into five parts bordering the infarction zone or normal region. We used Western blotting, quantitative RT-PCR, immunofluorescence, immunohistochemistry and Masson’s trichrome staining to explore the function of S100A4. Results: We found significant increases of S100A4 level and cardiac fibrosis markers, and β-catenin signaling activation in vitro and in vivo. In addition, knockdown of S100A4 significantly reduced cardiac fibrosis and β-catenin levels. Moreover, the expression of S100A4 decreased after ICG-001 inhibited β-catenin signal pathway. Conclusion: Downregulation of S100A4 alleviates cardiac fibrosis via Wnt/β -catenin pathway in mice. S100A4 may be a therapeutic target of cardiac fibrosis.