TAX1BP1 overexpression attenuates cardiac dysfunction and remodeling in STZ-induced diabetic cardiomyopathy in mice by regulating autophagy
TAX1BP1 overexpression attenuates cardiac dysfunction and remodeling in STZ-induced diabetic cardiomyopathy in mice by regulating autophagy
复制标题
TAX1BP1过表达通过调节自噬减轻STZ诱导的小鼠糖尿病心肌病的心脏功能障碍和重塑
DOI：
10.1016/j.bbadis.2018.02.012
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发表时间：
2018-05-01
影响因子：
6.2
通讯作者：
Tang, Qi Zhu
中科院分区：
文献类型：
--
作者：
Xiao, Yang;Wu, Qing Qing;Tang, Qi Zhu
糖尿病心肌病与心脏自噬抑制和炎症加剧有关。紫杉醇结合蛋白 1 (TAXIBP1) 对自噬和炎症的影响表明它可能参与糖尿病心肌病的进展。给小鼠注射链脲佐菌素（STZ）以诱导实验性糖尿病。注射 STZ 12 周后，使用腺病毒系统诱导心脏特异性 TAX1BP1 过度表达。STZ 诱导的糖尿病小鼠心脏中 TAXI BPI 表达显着降低。 TAXI BPI 在心脏中的过度表达可减轻 STZ 诱导的糖尿病小鼠的心脏肥大和纤维化，减轻炎症、氧化应激和细胞凋亡，并改善心脏功能。糖尿病小鼠表现出自噬减少。相比之下，在过度表达 TAX1BP1 的糖尿病小鼠中观察到自噬增加。 TAXIBP1 过表达促进自噬通量，体外 LC3-RFP 荧光增加证明了这一点。此外，自噬抑制剂3-MA消除了TAXIBP1的体内保护作用。有趣的是，我们发现 TABP1.通过激活非经典 NF-KB 信号通路来增加自噬。相反，ReIB 敲低破坏了 TAX1BP1 对心肌细胞的保护作用。因此，TAX1BP1 可以恢复降低的自噬水平，从而减少炎症反应和氧化应激，并减少心肌细胞的凋亡。
Diabetic cardiomyopathy is associated with suppressed autophagy and augmented inflammation in the heart. The effects of Taxl binding protein 1 (TAXIBP1) on both autophagy and inflammation suggest that it may participate in the progression of diabetic cardiomyopathy. Mice were injected with streptozotocin (STZ) to induce experimental diabetes. An adenovirus system was used to induce heart specific TAX1BP1 overexpression 12 weeks after STZ injection.TAXI BPI expression was significantly decreased in STZ-induced diabetic mouse hearts. TAXI BPI over expression in the heart alleviated cardiac hypertrophy and fibrosis, attenuated inflammation, oxidative stress, and apoptosis, and improved cardiac function in STZ-induced diabetic mice. Diabetic mice exhibited decreased autophagy. By contrast, increased autophagy was observed in diabetic mice overexpressing TAX1BP1. TAXIBP1 overexpression promoted autophagic flux, as demonstrated by increased LC3-RFP fluorescence in vitro. Furthermore, the autophagy inhibitor 3-MA abolished the protective effects of TAXIBP1 in vivo. Interestingly, we found that TABP1. increased autophagy via the activation of a non-canonical NF-KB signaling pathway. Conversely, ReIB knockdown disrupted the protective effects of TAX1BP1 in cardiomyocytes. TAX1BP1 thus restores the decreased autophagy level, leading to decreased inflammatory responses and oxidative stress and reduced apoptosis in cardiomyocytes.