Zhang Xian, Sha Minglei, Yao Yuting, Da Jia, Jing Dadao
Department of Geriatrics, Shanghai First People's Hospital, Shanghai 200080, P.R. China.
Mol Med Rep. 2015 Nov;12(5):6761-7. doi: 10.3892/mmr.2015.4247. Epub 2015 Aug 25.
Chronic heart failure (CHF) is the final stage of various heart diseases, and is increasingly recognized as a major health problem in the elderly. Previous studies demonstrated that B‑type‑natriuretic peptide (BNP) is an established biomarker of CHF. Furthermore, BNP also regulates cell proliferation, differentiation and apoptosis. Recent evidence has revealed that BNP affects myocardial cell apoptosis during myocardial ischemia‑reperfusion injury. Long non‑coding RNAs (lncRNAs) are emerging as novel molecular compounds involved in gene regulation, and have important roles in numerous human diseases. However, the mechanism underlying the BNP and lncRNA-induced regulation of myocardial cell apoptosis remains to be elucidated. The present study reported that lncRNA LSINCT5, upregulated by BNP, is able to regulate myocardial cell apoptosis via the activation of the caspase‑1/interleukin (IL)‑1β signaling pathway. BNP-induced apoptosis of HCM cells was observed using flow cytometry, and involved caspase‑1. In addition, expression profiling using a human lncRNA polymerase chain reaction array revealed that LSINCT5 was highly expressed in BNP-treated myocardial cells, as compared with untreated cells. The role of lncRNA LSINCT5 in HCM cell apoptosis was also investigated. The results of the present study indicated that LSINCT5 silencing by small interfering RNA inhibits caspase‑1/IL‑1β signaling, and suppresses apoptosis in BNP-treated HCM cells. Therefore, high expression levels of BNP promote the apoptosis of myocardial cells through the lncRNA LSINCT5 mediator, which activates the caspase‑1/IL‑1β signaling pathway. These findings uncovered a novel pathogenic mechanism, and provided a potential therapeutic target for CHF.
慢性心力衰竭(CHF)是各种心脏病的终末阶段,并且越来越被认为是老年人中的一个主要健康问题。先前的研究表明,B型利钠肽(BNP)是CHF的一种公认的生物标志物。此外,BNP还调节细胞增殖、分化和凋亡。最近的证据显示,BNP在心肌缺血-再灌注损伤期间影响心肌细胞凋亡。长链非编码RNA(lncRNA)作为参与基因调控的新型分子化合物正在兴起,并且在多种人类疾病中发挥重要作用。然而,BNP和lncRNA诱导的心肌细胞凋亡调控机制仍有待阐明。本研究报道,由BNP上调的lncRNA LSINCT5能够通过激活半胱天冬酶-1/白细胞介素(IL)-1β信号通路来调节心肌细胞凋亡。使用流式细胞术观察到BNP诱导的HCM细胞凋亡,并且涉及半胱天冬酶-1。此外,与人lncRNA聚合酶链反应阵列的表达谱分析显示,与未处理的细胞相比,LSINCT5在BNP处理的心肌细胞中高表达。还研究了lncRNA LSINCT5在HCM细胞凋亡中的作用。本研究结果表明,小干扰RNA使LSINCT5沉默可抑制半胱天冬酶-1/IL-1β信号传导,并抑制BNP处理的HCM细胞中的凋亡。因此,BNP的高表达水平通过lncRNA LSINCT5介导物促进心肌细胞凋亡,该介导物激活半胱天冬酶-1/IL-1β信号通路。这些发现揭示了一种新的致病机制,并为CHF提供了一个潜在的治疗靶点。