Identification of cell and disease specific microRNAs in glomerular pathologies
Identification of cell and disease specific microRNAs in glomerular pathologies
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DOI：
10.1111/jcmm.14270
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发表时间：
2019-06-01
影响因子：
5.3
通讯作者：
Schiffer, Mario
中科院分区：
文献类型：
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作者：
Mueller-Deile, Janina;Dannenberg, Jan;Schiffer, Mario
MicroRNA (miR) 是一种小型非编码 RNA，可调节生理过程和疾病中的基因表达。目前 miR 已被用于寻找与疾病有关的新机制，并且在未来，它们可能作为诊断标记。为了鉴定在肾小球疾病中发挥作用的 miR，尿液 miR 筛查是一种常用的工具。然而，在尿液中检测到的 miR 可能只是从血流中过滤出来，并且可能在身体的任何地方产生，因此它们可能与疾病完全无关。我们对不同肾小球疾病患者的合并尿液样本以及培养的人足细胞、人系膜细胞、人肾小球内皮细胞和人肾小管细胞进行了联合 miR 筛查。 The miR-screening in renal cells was done in untreated conditions and after stimulation with TGF-beta.检测到的调节 miR 的合并使我们能够识别疾病特异性、细胞类型特异性和细胞应激诱导的 miR。在所有细胞类型中，大多数 miR 在 TGF-β 刺激后均下调。对于大多数 miR，TGF-β 后 miR 的上调具有细胞类型特异性。此外，来自不同肾小球疾病患者的尿液 miR 可以分配给不同的肾细胞类型。大多数 miR 在一种疾病中受到特异性调节。与对照相比，所有疾病尿液中只有 miR-155 上调，因此似乎相当不具有特异性。总之，尿液和细胞 miR 筛查相结合可以改善筛查结果的解释。 These data are useful to identify novel miRs potentially involved in glomerular diseases.
MicroRNAs (miRs) are small non-coding RNAs that regulate gene expression in physiological processes as well as in diseases. Currently miRs are already used to find novel mechanisms involved in diseases and in the future, they might serve as diagnostic markers. To identify miRs that play a role in glomerular diseases urinary miR-screenings are a frequently used tool. However, miRs that are detected in the urine might simply be filtered from the blood stream and could have been produced anywhere in the body, so they might be completely unrelated to the diseases. We performed a combined miR-screening in pooled urine samples from patients with different glomerular diseases as well as in cultured human podocytes, human mesangial cells, human glomerular endothelial cells and human tubular cells. The miR-screening in renal cells was done in untreated conditions and after stimulation with TGF-beta. A merge of the detected regulated miRs led us to identify disease-specific, cell type-specific and cell stress-induced miRs. Most miRs were down-regulated following the stimulation with TGF-beta in all cell types. Up-regulation of miRs after TGF-beta was cell type-specific for most miRs. Furthermore, urinary miRs from patients with different glomerular diseases could be assigned to the different renal cell types. Most miRs were specifically regulated in one disease. Only miR-155 was up-regulated in all disease urines compared to control and therefore seems to be rather unspecific. In conclusion, a combined urinary and cell miR-screening can improve the interpretation of screening results. These data are useful to identify novel miRs potentially involved in glomerular diseases.