Tissue-Specific MicroRNA Expression Patterns in Four Types of Kidney Disease
Tissue-Specific MicroRNA Expression Patterns in Four Types of Kidney Disease
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DOI：
10.1681/asn.2016121280
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发表时间：
2017-10-01
影响因子：
13.6
通讯作者：
Liang, Mingyu
中科院分区：
文献类型：
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作者：
Baker, Maria Angeles;Davis, Seth J.;Liang, Mingyu
MicroRNA有助于肾脏疾病的发展。然而，以前对人类肾脏中microRNA表达的分析受到组织异质性或仅包括一种病理类型的限制。在这项研究中，我们使用激光捕获显微切割，获得肾小球和近端小管从98人肾穿刺活检标本microRNA表达分析，使用深度测序。我们分析了来自糖尿病肾病（DN）、FSGS、伊加肾病（IgAN）、膜增生性GN（MPGN）患者（每种疾病n=19-23）和对照组（n=14）的标本。与对照肾小球相比，DN、FSGS、IgAN和MPGN肾小球分别表现出18、12、2和17种已知microRNA的差异表达。几种microRNA的表达在不同疾病条件下也不同。具体来说，与对照或FSGS肾小球相比，IgAN肾小球表现出hsa-miR-3182表达下调。此外，hsa-miR-146 a-5 p和hsa-miR-30 a-5 p的表达水平将DN与除IgAN之外的所有其他条件区分开。与对照近端小管相比，DN，FSGS，IgAN和MPGN近端小管分别有13，14，8和8个microRNA的差异表达，但microRNA的表达在疾病条件之间没有显着差异。几种microRNA的丰度与肾功能指标相关。最后，我们在第二组DN（n=19）和FSGS（n=21）患者中验证了所选microRNA的肾小球差异表达。总之，我们确定了与几种肾脏病理相关的组织特异性microRNA表达模式。所鉴定的microRNA可作为肾脏疾病的生物标志物，并可能参与疾病的发病机制。
MicroRNAs contribute to the development of kidney disease. Previous analyses of microRNA expression in human kidneys, however, were limited by tissue heterogeneity or the inclusion of only one pathologic type. In this study, we used laser-capture microdissection to obtain glomeruli and proximal tubules from 98 human needle kidney biopsy specimens for microRNA expression analysis using deep sequencing. We analyzed specimens from patients with diabetic nephropathy (DN), FSGS, IgA nephropathy (IgAN), membranoproliferative GN (MPGN) (n=19-23 for each disease), and a control group (n=14). Compared with control glomeruli, DN, FSGS, IgAN, and MPGN glomeruli exhibited differential expression of 18, 12, two, and 17 known microRNAs, respectively. The expression of several microRNAs also differed between disease conditions. Specifically, compared with control or FSGS glomeruli, IgAN glomeruli exhibited downregulated expression of hsa-miR-3182. Furthermore, in combination, the expression levels of hsa-miR-146a-5p and hsa-miR-30a-5p distinguished DN from all other conditions except IgAN. Compared with control proximal tubules, DN, FSGS, IgAN, and MPGN proximal tubules had differential expression of 13, 14, eight, and eight microRNAs, respectively, but expression of microRNAs did not differ significantly between the disease conditions. The abundance of several microRNAs correlated with indexes of renal function. Finally, we validated the differential glomerular expression of select microRNAs in a second cohort of patients with DN (n=19) and FSGS (n=21). In conclusion, we identified tissue specific microRNA expression patterns associated with several kidney pathologies. The identified microRNAs could be developed as biomarkers of kidney diseases and might be involved in disease mechanisms.