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尿 SPP1 可能成为局灶节段性肾小球硬化症的一种非侵入性诊断标志物。

Urinary SPP1 has potential as a non-invasive diagnostic marker for focal segmental glomerulosclerosis.

机构信息

Department of Nephrology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, China.

Centre for Genomic and Personalized Medicine, Department of Immunology, School of Basic Medical Sciences, Guangxi Medical University, Nanning, 530021, China.

出版信息

FEBS Open Bio. 2023 Nov;13(11):2061-2080. doi: 10.1002/2211-5463.13704. Epub 2023 Sep 27.

DOI:10.1002/2211-5463.13704
PMID:37696527
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10626280/
Abstract

Focal segmental glomerulosclerosis (FSGS) is a type of chronic glomerular nephropathy showing characteristic glomerular sclerosis, diagnosed by kidney biopsy. However, it is difficult and expensive to monitor disease progression with repeated renal biopsy in clinical practice, and thus here we explored the feasibility of urine biomarkers as non-invasive diagnostic tools. We downloaded scRNA-seq datasets of 20 urine cell samples and 3 kidney tissues and obtained two gene lists encoding extracellular proteins for bioinformatic analysis; in addition, we identified key EP-Genes by immunohistochemical staining and performed bulk RNA sequencing with 12 urine samples. We report that urine cells and kidney cells were correlated. A total of 64 EP-Genes were acquired by intersecting genes of distal tubular cluster with extracellular proteins. Function enrichment analysis showed that EP-Genes might be involved in the immune response and extracellular components. Six key EP-Genes were identified and correlated with renal function. IMC showed that key EP-Genes were located mainly in tubules. Cross verification and examination of a urine RNAseq dataset showed that SPP1 had diagnostic potential for FSGS. The presence of urine SPP1 was primarily associated with macrophage infiltration in kidney, and the pathogenesis of FSGS may be related to innate immunity. Urinary cells seemed to be strongly similar to kidney cells. In summary, SPP1 levels reflect renal function and may have potential as a biomarker for non-invasive diagnosis of FSGS.

摘要

局灶节段性肾小球硬化症（FSGS）是一种以肾小球硬化为特征的慢性肾小球肾病，通过肾活检诊断。然而，在临床实践中，通过重复肾活检来监测疾病进展既困难又昂贵，因此我们在此探讨了尿液生物标志物作为非侵入性诊断工具的可行性。我们下载了 20 个尿液细胞样本和 3 个肾脏组织的 scRNA-seq 数据集，并获得了两个编码细胞外蛋白的基因列表，用于生物信息学分析；此外，我们通过免疫组织化学染色鉴定了关键的 EP 基因，并对 12 个尿液样本进行了批量 RNA 测序。我们报告说尿液细胞和肾脏细胞是相关的。通过与远端肾小管簇的基因交叉，获得了总共 64 个 EP 基因。功能富集分析表明，EP 基因可能参与免疫反应和细胞外成分。鉴定了 6 个关键的 EP 基因，与肾功能相关。IMC 显示关键的 EP 基因主要位于肾小管中。对尿液 RNAseq 数据集的交叉验证和检查表明，SPP1 对 FSGS 具有诊断潜力。尿液 SPP1 的存在主要与肾脏中的巨噬细胞浸润有关，FSGS 的发病机制可能与先天免疫有关。尿液细胞似乎与肾脏细胞非常相似。总之，SPP1 水平反映了肾功能，可能有作为 FSGS 非侵入性诊断的生物标志物的潜力。

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