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整合素β6亚基是糖尿病肾病患者急性肾损伤的潜在诊断标志物:单细胞测序数据分析

Integrin subunit beta 6 is a potential diagnostic marker for acute kidney injury in patients with diabetic kidney disease: a single cell sequencing data analysis.

作者信息

Yao Congcong, Li Ziwei, Su Hongshuang, Sun Keke, Liu Qihui, Zhang Yan, Zhu Lishuang, Jiang Feng, Fan Yaguang, Shou Songtao, Wu Heng, Jin Heng

机构信息

Department of Emergency Medicine, Tianjin Medical University General Hospital, Tianjin, China.

Department of Critical Care Medicine, Tianjin Medical University General Hospital, Tianjin, China.

出版信息

Ren Fail. 2024 Dec;46(2):2409348. doi: 10.1080/0886022X.2024.2409348. Epub 2024 Oct 2.

Abstract

BACKGROUND

Diabetic kidney disease (DKD), a prevalent complication of diabetes mellitus, is often associated with acute kidney injury (AKI). Thus, the development of preventive and therapeutic strategies is crucial for delaying the progression of AKI and DKD.

METHODS

The GSE183276 dataset, comprising the data of 20 healthy controls and 12 patients with AKI, was downloaded from the Gene Expression Omnibus (GEO) database to analyze the AKI group. For analyzing the DKD group, the GSE131822 dataset, comprising the data of 3 healthy controls and 3 patients with DKD, was downloaded from the GEO database. The common differentially expressed genes (DEGs) in renal tubular epithelial cells (TECs) were subjected to enrichment analyses. Next, a protein-protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes database to analyze gene-related regulatory networks. Finally, the AKI animal models and the DKD and AKI cell models were established, and the reliability of the identified genes was validated using quantitative real-time polymerase chain reaction analysis.

RESULTS

Functional analysis was performed with 40 common DEGs in TECs. Eight hub genes were identified using the PPI and gene-related networks. Finally, validation experiments with the animal model and the cellular model revealed the four common DEGs. Four DEGs that share molecular mechanisms in the pathogenesis of DKD and AKI were identified. In particular, the expression of Integrin Subunit Beta 6(, a hub and commonly upregulated gene, was upregulated in the models.

CONCLUSION

may serve as a biomarker for early AKI diagnosis in patients with DKD and as a target for early intervention therapies.

摘要

背景

糖尿病肾病(DKD)是糖尿病常见的并发症,常与急性肾损伤(AKI)相关。因此,制定预防和治疗策略对于延缓AKI和DKD的进展至关重要。

方法

从基因表达综合数据库(GEO)下载包含20例健康对照和12例AKI患者数据的GSE183276数据集,以分析AKI组。为分析DKD组,从GEO数据库下载包含3例健康对照和3例DKD患者数据的GSE131822数据集。对肾小管上皮细胞(TECs)中常见的差异表达基因(DEGs)进行富集分析。接下来,使用检索相互作用基因数据库的搜索工具构建蛋白质-蛋白质相互作用(PPI)网络,以分析基因相关的调控网络。最后,建立AKI动物模型以及DKD和AKI细胞模型,并使用定量实时聚合酶链反应分析验证所鉴定基因的可靠性。

结果

对TECs中的40个常见DEGs进行功能分析。使用PPI和基因相关网络鉴定出8个枢纽基因。最后,通过动物模型和细胞模型的验证实验揭示了4个常见的DEGs。确定了在DKD和AKI发病机制中具有共同分子机制的4个DEGs。特别是,整合素β6亚基(一种枢纽且普遍上调的基因)在模型中的表达上调。

结论

可能作为DKD患者早期AKI诊断的生物标志物以及早期干预治疗的靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e86/11448326/9ec659b915b3/IRNF_A_2409348_F0001_C.jpg

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