Autophagy activation attenuates angiotensin II-induced cardiac fibrosis
Autophagy activation attenuates angiotensin II-induced cardiac fibrosis
复制标题
DOI：
10.1016/j.abb.2015.11.001
复制
发表时间：
2016-01-15
影响因子：
3.9
通讯作者：
Jiang, Jianmin
中科院分区：
文献类型：
--
作者：
Liu, Shenglan;Chen, Shaorui;Jiang, Jianmin
自噬参与了许多疾病的发生过程。然而，自噬在心脏纤维化中的作用知之甚少。因此，我们在体外和体内检测血管紧张素II （Ang II）诱导的自噬是否对心脏纤维化具有调节作用。用透射电镜（TEM）、免疫荧光（immunofluorescence）和Western blot观察了经angii刺激的大鼠心脏成纤维细胞（CFs）的自噬活性。在注射angii的小鼠中，观察到LC3点与波形蛋白的共定位增加。在大鼠CFs中，与自噬诱导剂雷帕霉素（Rapa）共处理，Ang ii诱导I型胶原（Col-I）上调，纤维连接蛋白（FN）降低。相反，通过自噬抑制剂氯喹（CQ）抑制自噬，或通过特异性siRNA敲低自噬途径的关键成分ATG5，会加重Ang ii介导的Col-I和FN的积累。此外，在输注Ang II的C57 BL/6小鼠中，腹腔注射Rapa可改善Ang II诱导的心脏纤维化和心功能障碍，而CQ治疗不仅会加重Ang II介导的心脏纤维化和心功能障碍，还会损害心功能。这些发现表明，自噬可能发挥保护作用，以减轻多余的细胞外基质（ECM）在心脏的积累。(C) 2015爱思唯尔公司版权所有。
Autophagy has been involved in numerous diseases processes. However, little is known about the role of autophagy in cardiac fibrosis. Thus, whether or not angiotensin II (Ang II)-induced autophagy has a regulatory function on cardiac fibrosis was detected in vitro and in vivo. In rat cardiac fibroblasts (CFs) stimulated with Ang II, activated autophagy was observed using transmission electron microscopic analysis (TEM), immunofluorescence and Western blot. In Ang II-infused mice, increased co-localization of LC3 puncta with vimentin was observed. In rat CFs, co-treated with rapamycin (Rapa), an autophagy inducer, Ang II-induced the upregulation of type I collagen (Col-I), fibronectin (FN) was decreased. Conversely, inhibition of autophagy by chloroquine (CQ), an autophagy inhibitor, or knockdown of ATG5, a key component of the autophagy pathway by specific siRNA, aggravated Ang II-mediated the accumulation of Col-I and FN. Furthermore, in C57 BL/6 mice with Ang II infusion, intraperitoneal administration of Rapa ameliorated Ang II-induced cardiac fibrosis and cardiac dysfunction, while CQ treatment not only exacerbated Ang II-mediated cardiac fibrosis and cardiac dysfunction, but also impaired cardiac function. These findings suggest that autophagy may exert a protective role to attenuate excess extra cellular matrix (ECM) accumulation in the heart. (C) 2015 Elsevier Inc. All rights reserved.