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探讨肾结石与颈动脉粥样硬化之间的分子相互作用:asporin 作为一种潜在的生物标志物。

Exploring the molecular interactions between nephrolithiasis and carotid atherosclerosis: asporin as a potential biomarker.

机构信息

Department of Urology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, Jiangsu, 210029, P.R. China.

Department of Urology, Huashan Hospital, Fudan University, Shanghai, 200040, PR China.

出版信息

Urolithiasis. 2024 Nov 26;52(1):169. doi: 10.1007/s00240-024-01665-1.

Abstract

Increasing evidence suggested nephrolithiasis has a close linkage with carotid atherosclerosis (CAS), with Randall's plaque (RP) being a precursor to kidney stones. Our study aimed to examine the crosstalk genes and potential molecular mechanisms between RP and CAS. We obtained microarray data for RP and CAS from the Gene Expression Omnibus (GEO) and used weighted gene co-expression network analysis (WGCNA) and differential gene expression (DEG) analysis to identify shared genes. By integrating WGCNA and DEG analysis, Asporin (ASPN) was identified as the key gene connecting RP and CAS, with its diagnostic potential assessed via a receiver operating characteristic (ROC) curve. Immune infiltration studies showed a significant correlation between ASPN and various immune cells in RP and CAS. ASPN was found to be less expressed in RP and CAS tissues compared to normal tissues, as confirmed by immunohistochemistry (IHC) and quantitative reverse-transcription PCR (qRT-PCR). The rat model confirmed the human tissue findings. ASPN can elucidate the shared pathogenic mechanisms underlying the two conditions, including immune response and osteoblast differentiation.

摘要

越来越多的证据表明肾结石与颈动脉粥样硬化(CAS)密切相关,而 Randall 斑块(RP)是肾结石的前身。我们的研究旨在探讨 RP 和 CAS 之间的交流基因和潜在的分子机制。我们从基因表达综合数据库(GEO)中获得了 RP 和 CAS 的微阵列数据,并使用加权基因共表达网络分析(WGCNA)和差异基因表达(DEG)分析来识别共享基因。通过整合 WGCNA 和 DEG 分析,发现 Asporin(ASPN)是连接 RP 和 CAS 的关键基因,通过受试者工作特征(ROC)曲线评估其诊断潜力。免疫浸润研究表明,ASPN 与 RP 和 CAS 中的各种免疫细胞之间存在显著相关性。免疫组织化学(IHC)和定量逆转录聚合酶链反应(qRT-PCR)证实,与正常组织相比,RP 和 CAS 组织中 ASPN 的表达水平较低。大鼠模型证实了人类组织的发现。ASPN 可以阐明这两种情况的共同致病机制,包括免疫反应和成骨细胞分化。

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