Comparison of Kidney Transcriptomic Profiles of Early and Advanced Diabetic Nephropathy Reveals Potential New Mechanisms for Disease Progression
Comparison of Kidney Transcriptomic Profiles of Early and Advanced Diabetic Nephropathy Reveals Potential New Mechanisms for Disease Progression
复制标题
早期和晚期糖尿病肾病肾脏转录组图谱的比较揭示了疾病进展的潜在新机制
DOI：
10.2337/db19-0204
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发表时间：
2019-12-01
期刊：
影响因子：
7.7
通讯作者：
Wang, Niansong
中科院分区：
文献类型：
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作者：
Fan, Ying;Yi, Zhengzi;Wang, Niansong
为了确定介导糖尿病肾病（DN）进展的因素，我们对来自早期DN患者、晚期DN患者和来自肾切除术样本的正常肾组织的肾活检样本进行了RNA测序。一组在DN早期上调而在晚期下调的基因被证明在很大程度上具有肾保护作用，这些基因包括维甲酸途径和胰高血糖素样肽1受体中的基因。另一组在早期下调但在晚期DN中高度上调的基因主要由与肾脏疾病发病机制相关的基因组成，如与免疫反应和纤维化相关的基因。与估计肾小球滤过率（eGFR）的相关性表明，铁转运和细胞分化途径中的基因与eGFR呈正相关，而免疫反应和纤维化途径中的基因与eGFR呈负相关。与各种组织病理学特征的相关性也确定了与不同基因本体论途径的关联。RNA测序数据集的反褶积分析表明，单核细胞、成纤维细胞和肌成纤维细胞在晚期DN肾脏中显著增加。因此，我们的研究提供了DN进展的潜在分子机制，以及在早期和晚期DN患者中观察到的差异基因表达与功能和结构变化的关联。
To identify the factors mediating the progression of diabetic nephropathy (DN), we performed RNA sequencing of kidney biopsy samples from patients with early DN, advanced DN, and normal kidney tissue from nephrectomy samples. A set of genes that were upregulated at early but downregulated in late DN were shown to be largely renoprotective, which included genes in the retinoic acid pathway and glucagon-like peptide 1 receptor. Another group of genes that were downregulated at early but highly upregulated in advanced DN consisted mostly of genes associated with kidney disease pathogenesis, such as those related to immune response and fibrosis. Correlation with estimated glomerular filtration rate (eGFR) identified genes in the pathways of iron transport and cell differentiation to be positively associated with eGFR, while those in the immune response and fibrosis pathways were negatively associated. Correlation with various histopathological features also identified the association with the distinct gene ontological pathways. Deconvolution analysis of the RNA sequencing data set indicated a significant increase in monocytes, fibroblasts, and myofibroblasts in advanced DN kidneys. Our study thus provides potential molecular mechanisms for DN progression and association of differential gene expression with the functional and structural changes observed in patients with early and advanced DN.