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肾小球毛细血管对 HLA 类 I 抗体的体外和体内 miRNA 反应。

Glomerulocapillary miRNA response to HLA-class I antibody in vitro and in vivo.

机构信息

Institute for Transfusion Medicine, University Hospital Essen, University Duisburg-Essen, Essen, Germany.

Immune Evaluation Laboratory, Department of Surgery, Baylor College of Medicine, Houston, TX, USA.

出版信息

Sci Rep. 2017 Nov 6;7(1):14554. doi: 10.1038/s41598-017-14674-5.

DOI:10.1038/s41598-017-14674-5
PMID:29109529
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5673998/
Abstract

UNLABELLED

Changes in miRNA expression glomerular of capillaries during antibody-mediated rejection (ABMR) are poorly understood and could contribute to the deleterious inflammation and fibrosis of ABMR via suppression of target genes. A better understanding could lead to novel diagnostic tools and reveal novel therapeutic targets. We explored deregulated miRNAs in an glomeruloendothelial in vitro model of ABMR due to class I human leukocyte antigen (HLA) with and without complement activation. We studied a set of 16 promising candidate miRNAs in microdissected glomeruli a confirmation set of 20 human transplant biopsies (DSA+) compared to 10 matched controls without evidence for ABMR. Twelve out of these 16 glomerulocapillary miRNAs could successfully be confirmed as dysregulated in vivo with 10 upregulated (let-7c-5p, miR-28-3p, miR-30d-5p, miR-99b-5p, miR-125a-5p, miR-195-5p, miR-374b-3p, miR-484, miR-501-3p, miR-520e) and 2 downregulated (miR29b-3p, miR-885-5p) in DSA+ vs.

CONTROLS

A random forest analysis based on glomerular miRNAs identified 18/20 DSA+ and 8/10 controls correctly. This glomerulocapillary miRNA signature associated with HLA class I-DSA could improve our understanding of ABMR and be useful for diagnostic or therapeutic purposes.

摘要

未加标签

抗体介导的排斥反应(ABMR)期间肾小球毛细血管中 miRNA 表达的变化知之甚少,通过抑制靶基因,可能导致 ABMR 的有害炎症和纤维化。更好的理解可能导致新的诊断工具,并揭示新的治疗靶点。我们在体外肾小球内皮 ABMR 模型中探索了因 HLA 类 I 而失调的 miRNA,同时也有和没有补体激活。我们研究了一组 16 个有前途的候选 miRNA,在微切割肾小球中的一个确认组 20 个人移植活检(DSA+)与 10 个匹配的无 ABMR 证据的对照相比。这 16 个肾小球毛细血管 miRNA 中有 12 个可以成功地在体内被证实为失调,其中 10 个上调(let-7c-5p、miR-28-3p、miR-30d-5p、miR-99b-5p、miR-125a-5p、miR-195-5p、miR-374b-3p、miR-484、miR-501-3p、miR-520e)和 2 个下调(miR29b-3p、miR-885-5p)在 DSA+vs.对照组中。

对照

基于肾小球 miRNA 的随机森林分析正确地识别了 18/20 个 DSA+和 8/10 个对照。这个与 HLA 类 I-DSA 相关的肾小球毛细血管 miRNA 特征可以提高我们对 ABMR 的理解,并有助于诊断或治疗目的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a15/5673998/28ad48072071/41598_2017_14674_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a15/5673998/34d5e28c706b/41598_2017_14674_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a15/5673998/28ad48072071/41598_2017_14674_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a15/5673998/34d5e28c706b/41598_2017_14674_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a15/5673998/a146d026c46f/41598_2017_14674_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a15/5673998/da1ae2c0b658/41598_2017_14674_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a15/5673998/434479baad5e/41598_2017_14674_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a15/5673998/28ad48072071/41598_2017_14674_Fig5_HTML.jpg

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