Zhang Tie-Ning, Goodwin Julie E, Liu Bing, Li Da, Wen Ri, Yang Ni, Xia Jing, Zhou Han, Zhang Tao, Song Wen-Liang, Liu Chun-Feng
Department of Pediatrics, PICU, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, 110004, China.
Department of Pediatrics, Yale University School of Medicine, New Haven, CT, USA; Department of Vascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, CT, USA.
Mol Ther Nucleic Acids. 2019 Sep 6;17:852-866. doi: 10.1016/j.omtn.2019.07.020. Epub 2019 Aug 5.
Septic shock with heart dysfunction is very common in intensive care units. However, whether long noncoding RNA (lncRNA) and mRNA profiles differ between patients with and without myocardial depression is unknown. We generated rat models of hypodynamic septic shock induced by lipopolysaccharide. A total of 12 rat models was constructed and heart tissue from each was collected. Whole genomic RNA sequencing was performed on left ventricular tissue; 6,508 novel lncRNAs and 432 annotated lncRNAs were identified in heart samples, and 74 lncRNAs were expressed differently in the sepsis and control groups. Gene ontology term enrichment indicated apoptosis and its related pathways showed obvious enrichment, which suggested cell apoptosis could play a critical role in the process of myocardial depression. Furthermore, we focused on one lncRNA from the Pvt1 gene. By silencing this lncRNA, we demonstrated knockdown of Pvt1 expression could induce cell apoptosis in lipopolysaccharide-induced heart cells, through increasing the expression of c-Myc, Bid, Bax, and caspase-3 and decreasing the expression of Myd88 and Bcl-2, thereby proving its functional role in myocardial depression. These results demonstrate that lncRNAs both participate in and mediate the pathological process of myocardial depression. Our study improves the understanding of the basic molecular mechanisms underlying myocardial depression.
感染性休克合并心功能障碍在重症监护病房非常常见。然而，有心肌抑制和无心肌抑制的患者之间长链非编码RNA（lncRNA）和mRNA谱是否存在差异尚不清楚。我们构建了脂多糖诱导的低动力性感染性休克大鼠模型。共构建了12个大鼠模型，并收集了每个模型的心脏组织。对左心室组织进行全基因组RNA测序；在心脏样本中鉴定出6508个新的lncRNA和432个已注释的lncRNA，且74个lncRNA在脓毒症组和对照组中的表达存在差异。基因本体术语富集表明凋亡及其相关途径有明显富集，这表明细胞凋亡可能在心肌抑制过程中起关键作用。此外，我们聚焦于Pvt1基因的一个lncRNA。通过沉默该lncRNA，我们证明敲低Pvt1表达可通过增加c-Myc、Bid、Bax和caspase-3的表达以及降低Myd88和Bcl-2的表达，诱导脂多糖诱导的心脏细胞凋亡，从而证明其在心肌抑制中的功能作用。这些结果表明lncRNA既参与又介导心肌抑制的病理过程。我们的研究增进了对心肌抑制潜在基本分子机制的理解。
