Abstract

Down-regulated lncRNA AC061961.2 in dilated cardiomyopathy (DCM) patients was previous reported. Whether AC061961.2 has regulatory effect on DCM still need exploration. Here, we tried to investigate the effect of AC061961.2 on DCM. After DCM model rat was established through injecting Adriamycin, left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), left ventricular ejection fraction (LVEF), and left ventricular fractional shortening (LVFS) were measured by echocardiography. Histopathological changes and apoptosis were detected by hematoxylin-eosin, Masson staining, and TUNEL. After cardiomyocytes were isolated and identified by immunofluorescence, DCM cell model was established by injecting adriamycin. After transfected with overexpressed-AC061961.2 plasmids, cell apoptosis was detected by flow cytometry. The expressions of AC061961.2, β-catenin, Axin2, c-Myc, CRP78, CHOP, Caspase-3, Bcl-2, and Bax in cardiomyocytes and heart tissues were detected by RT-qPCR or western blot. LVEDD and LVESD were increased while LVEF and LVFS were decreased in DCM rats. The histopathological of heart tissues showed a typical sign of DCM. Apoptosis were increased in heart tissues of DCM rats. In DCM rats, the expressions of AC061961.2, β-catenin, Axin2, c-Myc, and Bcl-2 were decreased, the expressions of CRP78, CHOP, Caspase-3, and Bax were increased. After the overexpression of AC061961.2, levels of β-catenin, Axin2, c-Myc, and Bcl-2 were increased, while levels of CRP78, CHOP, Caspase-3, and Bax were decreased, compared with that in DCM cardiomyocytes. LncRNA AC061961.2 overexpression inhibited endoplasmic reticulum stress induced apoptosis in DCM rats and cardiomyocytes via activating Wnt/β-catenin pathway.

摘要

先前报道了扩张型心肌病（DCM）患者中下调的lncRNA AC061961.2。AC061961.2是否对DCM有调节作用仍需探索。在这里，我们试图研究 AC061961.2 对 DCM 的影响。通过注射阿霉素建立DCM模型大鼠后，超声心动图测量左心室舒张末期直径（LVEDD）、左心室收缩末期直径（LVESD）、左心室射血分数（LVEF）和左心室缩短率（LVFS） . 苏木精-伊红、Masson染色和TUNEL检测组织病理学改变和细胞凋亡。经免疫荧光分离鉴定心肌细胞后，注射阿霉素建立DCM细胞模型。转染过表达的AC061961.2质粒后，流式细胞仪检测细胞凋亡。RT-qPCR或western blot检测心肌细胞和心脏组织中AC061961.2、β-catenin、Axin2、c-Myc、CRP78、CHOP、Caspase-3、Bcl-2和Bax的表达。DCM 大鼠 LVEDD 和 LVESD 增加，而 LVEF 和 LVFS 降低。心脏组织病理学表现为典型的DCM征象。DCM大鼠心脏组织细胞凋亡增加。DCM大鼠中AC061961.2、β-catenin、Axin2、c-Myc、Bcl-2表达降低，CRP78、CHOP、Caspase-3、Bax表达升高。与 DCM 心肌细胞相比，过表达 AC061961.2 后，β-catenin、Axin2、c-Myc 和 Bcl-2 水平升高，而 CRP78、CHOP、Caspase-3 和 Bax 水平降低。LncRNA AC061961。通过激活 Wnt/β-catenin 通路。