PDF(Pubmed)
Abstract：
Long non-coding RNA RP11-64B16.4 (myocardial infarction protection-related lncRNA [MIPRL]) is among the most abundant and the most upregulated lncRNAs in ischemic human hearts. However, its role in ischemic heart disease is unknown. We found MIPRL was conserved between human and mouse and its expression was increased in mouse hearts after acute myocardial infarction (AMI) and in cultured human and mouse cardiomyocytes after hypoxia. The infarcted size, cardiac cell apoptosis, cardiac dysfunction, and cardiac fibrosis were aggravated in MIPRL knockout mice after AMI. The above adverse results could be reversed by re-expression of MIPRL via adenovirus expressing MIPRL. Both in vitro and in vivo, we identified that heat shock protein beta-8 (HSPB8) was a target gene of MIPRL, which was involved in MIPRL-mediated anti-apoptotic effects on cardiomyocytes. We further discovered that MIPRL could combine with the messenger RNA (mRNA) of HSPB8 and increase its expression in cardiomyocytes by enhancing the stability of HSPB8 mRNA. In summary, we have found for the first time that the ischemia-enhanced lncRNA MIPRL protects against AMI via its target gene HSPB8. MIPRL might be a novel promising therapeutic target for ischemic heart diseases such as AMI.
摘要：
长链非编码RNARP11-64B16.4（心肌梗塞保护相关的lncRNA[MIPRL]）是缺血性人类心脏中最丰富和最上调的lncRNA之一。然而,其在缺血性心脏病中的作用尚不清楚。我们发现MIPRL在人和小鼠之间是保守的，并且其在急性心肌梗塞（AMI）后的小鼠心脏以及缺氧后的培养的人和小鼠心肌细胞中的表达增加。梗死面积,心肌细胞凋亡，心功能不全,MIPRL基因敲除小鼠AMI后心肌纤维化加重。通过表达MIPRL的腺病毒再表达MIPRL可以逆转上述不利结果。在体外和体内，我们确定热休克蛋白β-8（HSPB8）是MIPRL的靶基因，参与MIPRL介导的心肌细胞抗凋亡作用。我们进一步发现MIPRL可以与HSPB8的信使RNA（mRNA）结合，并通过增强HSPB8mRNA的稳定性来增加其在心肌细胞中的表达。总之,我们首次发现缺血增强的lncRNAMIPRL通过其靶基因HSPB8保护AMI。MIPRL可能是缺血性心脏病如AMI的新的有希望的治疗靶点。
