Involvement of microRNA-23b-5p in the promotion of cardiac hypertrophy and dysfunction via the HMGB2 signaling pathway
Involvement of microRNA-23b-5p in the promotion of cardiac hypertrophy and dysfunction via the HMGB2 signaling pathway
复制标题
microRNA-23b-5p 通过 HMGB2 信号通路参与促进心脏肥大和功能障碍。
DOI：
10.1016/j.biopha.2019.108977
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发表时间：
2019-08-01
影响因子：
7.5
通讯作者：
Yu, Fei
中科院分区：
文献类型：
--
作者：
Oumarou, Diafara Boureima;Ji, Heyu;Yu, Fei
心肌细胞向肥大进展及其逐渐转变为心力衰竭的过程代表了一种多因素的健康障碍。本研究的目的是确定 miR-23b-5p 异常过度表达及其通过 HMGB2 促进心脏肥大和功能障碍的分子机制。在胸主动脉缩窄 (TAC)/血管紧张素-II (Ang-II) 诱导的心功能障碍条件下，采用 9 型重组腺相关病毒 (rAAV9) 来操纵 miR-23b-5p 表达。通过超声心动图和有创压力容量分析评估心脏结构和功能。通过蛋白质印迹法检测心脏肥大条件下HMGB2的表达。使用荧光素酶报告载体、包含miR-23b-5p模拟序列的慢病毒构建体和微小RNA抑制剂（miR抑制剂）验证miR-23b-5p和HMGB2之间的生化关系。在 Ang-II 和 TAC 诱导的心脏肥大条件下，心脏中 miR-23b-5p 的表达水平均增加。荧光素酶活性分析结果表明，HMGB2 是 miR-23b-5p 的假定靶点。 miR-23b-5p 体内过表达会加剧压力超负荷引起的心脏肥大和功能障碍，而 miR 抑制剂则增加 HMGB2 表达并逆转这些影响。在本研究中，我们观察到miR-23b-5p通过HMGB2信号通路介导并参与心脏肥大和功能障碍的加重。
The processes involved in the progression of myocardial cells towards hypertrophy and its gradual transition to heart failure represent a multifactorial health disorder. The aim of this study was to identify the molecular mechanism(s) underlying the abnormal overexpression of miR-23b-5p and its involvement in the promotion of cardiac hypertrophy and dysfunction via HMGB2. A type 9 recombinant adeno-associated virus (rAAV9) was employed to manipulate miR-23b-5p expression under conditions of thoracic aortic constriction (TAC)-/angiotensin-II (Ang-II)-induced cardiac dysfunction. Cardiac structures and functions were assessed by echocardio-graphy and invasive pressure-volume analysis. HMGB2 expression under conditions of cardiac hypertrophy was detected by western blotting. The biochemical relationship between miR-23b-5p and HMGB2 was verified using a luciferase reporter vector, lentiviral construct comprising the miR-23b-5p mimic sequence, and microRNA inhibitor (miR-inhibitor). The expression levels of miR-23b-5p were increased in the hearts under conditions of both Ang-II- and TAC-induced cardiac hypertrophy. The results of the luciferase activity analysis showed that HMGB2 is a supposed target of miR-23b-5p. miR-23b-5p overexpression in vivo aggravated pressure overload-induced cardiac hypertrophy and dysfunction, whereas the miR-inhibitor increased HMGB2 expression and reversed these effects. In the present study, we observed that miR-23b-5p mediates and is involved in the aggravation of cardiac hypertrophy and dysfunction via the HMGB2 signaling pathway.