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化脓性汗腺炎中 microRNA 效应器 RNA 诱导沉默复合物:活跃炎症病变内的显著失调。

The microRNA effector RNA-induced silencing complex in hidradenitis suppurativa: a significant dysregulation within active inflammatory lesions.

机构信息

Department of Dermatology, Venereology and Allergology, Ruhr-University Bochum, Gudrunstr. 56, 44791, Bochum, Germany.

出版信息

Arch Dermatol Res. 2017 Sep;309(7):557-565. doi: 10.1007/s00403-017-1752-1. Epub 2017 Jun 20.

Abstract

Recently, we could show that the expression levels of the key regulators of the microRNA (miRNA) maturation and transport were dysregulated in inflamed hidradenitis suppurativa (HS) tissue (Heyam et al. in Wiley Interdiscip Rev RNA 6:271-289, 2015). The RNA-induced silencing complex (RISC) is the central element of the miRNA pathway and regulates miRNA formation and function. We investigated the expression of the RISC components, namely transactivation-responsive RNA-binding protein-1 (TRBP1), TRBP2, protein activator (PACT) of the interferon-induced protein kinase R, Argonaute RISC Catalytic Component-1 (AGO1) and Component-2 (AGO2), metadherin, and staphylococcal nuclease and Tudor domain-containing-1 (SND1) in inflamed HS tissue compared to healthy and psoriatic controls by real-time reverse transcription polymerase chain reaction. Expression levels of all investigated components were significantly lower in lesional HS skin (n = 18) compared to healthy controls (n = 10). TRBP1, PACT, AGO1, AGO2, and SND1 expression levels were significantly down-regulated in lesional HS skin compared to healthy-appearing perilesional skin (n = 7). TRBP2 and SND1 expression levels were significantly lower in healthy-appearing perilesional skin compared to healthy controls. In lesional HS skin, expression levels of PACT, AGO1, and AGO2 were significantly lower compared to psoriatic skin (n = 10). In summary, our data showed that all investigated components of RISC are dysregulated in the skin of HS patients, providing support for the hypothesis that miRNAs may have a pathological role in the inflammatory pathogenesis of HS.

摘要

最近,我们能够证明,在炎症性化脓性汗腺炎(HS)组织中,miRNA(miRNA)成熟和运输的关键调节剂的表达水平失调(Heyam 等人,Wiley Interdiscip Rev RNA 6:271-289,2015)。RNA 诱导沉默复合物(RISC)是 miRNA 途径的核心元件,调节 miRNA 的形成和功能。我们通过实时逆转录聚合酶链反应,研究了 RISC 成分,即转录激活反应性 RNA 结合蛋白 1(TRBP1)、TRBP2、干扰素诱导蛋白激酶 R 的蛋白激活剂(PACT)、Argonaute RISC 催化成分 1(AGO1)和成分 2(AGO2)、metadherin 和葡萄球菌核酸酶和 Tudor 结构域包含蛋白 1(SND1)在炎症性 HS 组织中的表达与健康和银屑病对照相比。与健康对照(n=10)相比,所有研究成分在病变性 HS 皮肤(n=18)中的表达水平均显著降低。与健康表现的病变周围皮肤(n=7)相比,病变性 HS 皮肤中的 TRBP1、PACT、AGO1、AGO2 和 SND1 表达水平明显下调。与健康对照相比,健康表现的病变周围皮肤中的 TRBP2 和 SND1 表达水平明显较低。在病变性 HS 皮肤中,与银屑病皮肤(n=10)相比,PACT、AGO1 和 AGO2 的表达水平明显较低。总之,我们的数据表明,RISC 的所有研究成分在 HS 患者的皮肤中失调,为 miRNA 可能在 HS 的炎症发病机制中具有病理作用的假说提供了支持。

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