在无反应的狼疮性肾炎患者中,计算机分析突出了上皮到间质转化特征的升高。

IF 1.9 4区 医学 Q3 RHEUMATOLOGY
Lupus Pub Date : 2025-10-01 Epub Date: 2025-08-01 DOI:10.1177/09612033251366405
Hyunsik Kim, Kyu-Hye Chun, Ho-Geun Yoon, Sungryul Yu, Jung-Yoon Yoo
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引用次数: 0

摘要

目的:狼疮性肾炎(LN)是系统性红斑狼疮(SLE)患者的常见并发症。作为一种慢性自身免疫性疾病,LN导致肾功能衰竭,严重影响患者的生活质量和死亡率。目前的LN治疗主要涉及传统的免疫抑制剂,如硫唑嘌呤和霉酚酸酯(MMF)。然而,一小部分患者对这些疗法的反应性较差。方法为了鉴定无应答组特异性上调的基因,我们分析了LN患者小管间质区域的rna测序数据和无应答LN患者的单细胞rna测序数据,使用了来自公共数据库的数据集。结果该分析显示LN患者的上皮-间质转化(EMT)特征增加,并确定COL3A1、TNC和PDGFRA是普通LN患者和无应答LN患者中常见的上调基因。单细胞rna测序进一步证实,这些基因主要在肾小管上皮细胞中表达。此外,对另外三个独立LN数据集的分析证实,COL3A1、TNC和PDGFRA在其他LN患者队列的小管间质区域显著上调。本研究提示无应答组可能表现出增强的EMT特征,特别是涉及到小管间质区域COL3A1、TNC和PDGFRA的上调。因此,这些发现可能有助于识别难治性患者的潜在生物标志物,并为LN管理的可能治疗靶点提供有价值的见解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
In silico analysis highlights elevation of epithelial-to-mesenchymal transition characteristics in non-responding lupus nephritis patients.

ObjectiveLupus nephritis (LN) is a common complication in a significant proportion of systemic lupus erythematosus (SLE) patients. As a chronic autoimmune disease, LN leads to renal failure, substantially impacting patient quality of life and mortality rates. Current LN treatments primarily involve traditional immunosuppressants, such as azathioprine and mycophenolate mofetil (MMF). However, a subset of patients exhibits poor responsiveness to these therapies.MethodsTo identify genes specifically upregulated in this non-responder group, we analyzed RNA-sequencing data from the tubulointerstitial regions of LN patients and single-cell RNA-sequencing data from non-response LN patients, using datasets obtained from public databases. ResultsThis analysis revealed an increased epithelial-to-mesenchymal transition (EMT) signature in the LN patients, and identified COL3A1, TNC, and PDGFRA as commonly upregulated genes in both general LN patients and non-responder LN patients. Further validation using single-cell RNA-sequencing confirmed that these genes are predominantly expressed in renal tubular epithelial cells. Furthermore, analysis of three additional independent LN datasets confirmed that COL3A1, TNC, and PDGFRA were significantly upregulated in the tubulointerstitial regions of other LN patient cohorts. ConclusionThis study suggests that the non-responder group may exhibit enhanced EMT features, particularly involving the upregulation of COL3A1, TNC, and PDGFRA in the tubulointerstitial region. Therefore, these findings may aid in identifying potential biomarkers for difficult-to-treat patients and offer valuable insights into possible therapeutic targets for LN management.

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来源期刊
Lupus
Lupus 医学-风湿病学
CiteScore
4.20
自引率
11.50%
发文量
225
审稿时长
1 months
期刊介绍: The only fully peer reviewed international journal devoted exclusively to lupus (and related disease) research. Lupus includes the most promising new clinical and laboratory-based studies from leading specialists in all lupus-related disciplines. Invaluable reading, with extended coverage, lupus-related disciplines include: Rheumatology, Dermatology, Immunology, Obstetrics, Psychiatry and Cardiovascular Research…
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