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血小板 microRNAs:从血小板生物学到可能的疾病生物标志物和治疗靶点。

Platelet microRNAs: From platelet biology to possible disease biomarkers and therapeutic targets.

机构信息

Cardiology Clinic, Democritus University of Thrace , Alexandroupolis , Greece.

出版信息

Platelets. 2013;24(8):579-89. doi: 10.3109/09537104.2012.724483. Epub 2012 Sep 20.

Abstract

Although anucleated, platelets contain megakaryocyte-derived messenger ribonucleic acid (mRNA) which can be translated to produce protein molecules. Recently, platelets have been found to contain small (∼23 base pair) non-coding microRNAs (miRNAs) derived from hairpin-like precursors. MiRNAs can specifically silence their mRNA targets regulating mRNA translation. Platelet miRNAs are reported to bind to important platelet target mRNAs involved in platelet reactivity including P2Y12 ADP receptor, GPIIb receptor, and cyclic AMP-dependent protein kinase A. They also regulate important functions such as platelet shape change, granules secretion, and platelet activation. Platelet miRNAs were also proposed as biomarkers of arteriosclerosis, although their role in vascular inflammation needs to be elucidated. Further, the possibility of using miRNAs as therapeutic tools has emerged. Using synthetic oligo-nucleotides that antagonize miRNAs binding to their mRNAs-targets or synthetic miRNAs mimics that enhance endogenous miRNAs function potentially will ultimately lead to the manipulation of platelet miRNAs expression and function with significant effects on specific protein levels and overall platelet reactivity.

摘要

尽管血小板没有细胞核,但其中含有巨核细胞衍生的信使 RNA(mRNA),这些 mRNA 可以被翻译为产生蛋白质分子。最近,人们发现血小板中含有源自发夹样前体的小(约 23 个碱基对)非编码 microRNA(miRNA)。miRNA 可以特异性地沉默其 mRNA 靶标,从而调节 mRNA 翻译。据报道,血小板 miRNA 可以与重要的血小板靶标 mRNA 结合,这些靶标 mRNA 参与血小板反应性,包括 P2Y12 ADP 受体、GPIIb 受体和环磷酸腺苷依赖性蛋白激酶 A。它们还调节重要的功能,如血小板形态变化、颗粒分泌和血小板激活。血小板 miRNA 也被提出作为动脉粥样硬化的生物标志物,尽管它们在血管炎症中的作用仍需阐明。此外,使用 miRNA 作为治疗工具的可能性已经出现。使用与 miRNA 结合其 mRNA 靶标的反义寡核苷酸或模拟内源性 miRNA 功能的合成 miRNA,可能会最终导致对血小板 miRNA 表达和功能的操纵,从而对特定蛋白质水平和整体血小板反应性产生显著影响。

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