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The Role of miRNAs in the Pathophysiology of Liver Diseases and Toxicity

机译:miRNA在肝脏疾病和毒性的病理生理中的作用

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摘要

Both acute and chronic liver toxicity represents a major global health burden and an important cause of morbidity and lethality worldwide. Despite epochal progress in the treatment of hepatitis C virus infections, pharmacological treatment strategies for most liver diseases are still limited and new targets for prevention or treatment of liver disease are urgently needed. MicroRNAs (miRNAs) represent a new class of highly conserved small non-coding RNAs that are involved in the regulation of gene expression by targeting whole networks of so called “targets”. Previous studies have shown that the expression of miRNAs is specifically altered in almost all acute and chronic liver diseases. In this context, it was shown that miRNA can exert causal roles, being pro- or anti-inflammatory, as well as pro- or antifibrotic mediators or being oncogenes as well as tumor suppressor genes. Recent data suggested a potential therapeutic use of miRNAs by targeting different steps in the hepatic pathophysiology. Here, we review the function of miRNAs in the context of acute and chronic liver diseases. Furthermore, we highlight the potential role of circulating microRNAs in diagnosis of liver diseases and discuss the major challenges and drawbacks that currently prevent the use of miRNAs in clinical routine.
机译:急性和慢性肝毒性都代表着全球主要的健康负担,也是全世界发病率和致死率的重要原因。尽管在丙型肝炎病毒感染的治疗方面取得了巨大进展,但大多数肝脏疾病的药物治疗策略仍然有限,急需预防或治疗肝病的新目标。 MicroRNA(miRNA)代表了一类高度保守的小型非编码RNA,它们通过靶向所谓的“靶标”的整个网络参与基因表达的调控。先前的研究表明,miRNA的表达在几乎所有急性和慢性肝病中均发生了特异性改变。在这种情况下,已经表明miRNA可以发挥因果作用,是促炎的或抗炎的,以及促炎的或抗纤维化的介质,或者是癌基因以及抑癌基因。最近的数据表明,通过靶向肝病理生理学的不同步骤,miRNA的潜在治疗用途。在这里,我们回顾了在急性和慢性肝病背景下miRNA的功能。此外,我们重点介绍了循环微RNA在肝病诊断中的潜在作用,并讨论了目前阻止在临床常规中使用miRNA的主要挑战和弊端。

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