The Anti-apoptotic Role of 3'-Untranslational Region in Response to Angiotensin II via Mcl1 Expression.
The Anti-apoptotic Role of 3'-Untranslational Region in Response to Angiotensin II via Mcl1 Expression.
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DOI：
10.3389/fcell.2020.593955
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发表时间：
2020
影响因子：
5.5
通讯作者：
Lu Q
中科院分区：
文献类型：
--
作者：
Lyu D;Yan H;Chen L;Zhang L;Du Y;Ding L;Lu Q
髓样细胞白血病1（Myeloid cell leukemia 1，Mcl 1）是心肌中一种丰富的蛋白质，在心肌细胞纤维化和抗炎中发挥重要作用，以预防心力衰竭。然而，Mcl 1 3′-UTR是否具有心脏保护功能尚不清楚。血管紧张素II（Ang II）处理后，在成年小鼠心脏组织中观察到Mcl 1的下调。与体内结果一致，在血管紧张素II处理的新生心肌细胞中确定了Mcl 1表达的减少。从机制上讲，Mcl 1 3 '-UTR通过上调Mcl 1和具有G-补丁结构域和叉头相关结构域1（Aggf 1）的血管生成因子（发挥心脏保护作用）来阻止Ang II诱导的心脏细胞凋亡。我们的工作拓宽了基因治疗靶点的范围，并提供了一个新的见解，基因治疗策略涉及mRNAs的3′-UTR的应用。
Myeloid cell leukemia 1 (Mcl1), an abundant protein in the myocardium, plays an essential role in fibrosis and anti-inflammation in cardiomyocytes to prevent heart failure. However, whether Mcl1 3′-untranslated regions (3′-UTR) has the cardio-protecting function remains unclear. Down-regulation of Mcl1 was observed in adult mice heart tissues after Angiotensin II (Ang II) treatment. Consistent with in vivo results, the reduction of Mcl1 expression was identified in Ang II-treated neonatal cardiomyocytes. Mechanistically, Mcl1 3′-UTR prevented Ang II-induced cardiac apoptosis via up-regulation of Mcl1 and an angiogenic factor with a G-patch domain and a forkhead-associated domain 1 (Aggf1), which plays cardiac-protective role. Our work broadens the scope of gene therapy targets and provides a new insight into gene therapy strategies involving mRNAs’ 3′-UTRs application.