转录组
折叠变化
Wnt信号通路
基因
肾脏疾病
基因表达谱
医学
生物
基因表达
肾功能
内科学
癌症研究
内分泌学
生物信息学
遗传学
作者
Anvesha Srivastava,Mark Maienschein‐Cline,Richard Amdur,Katalin Suszták,Jeffrey B. Kopp,Haiming Cao,Divya Shankaranarayanan,Yoosif Abdalla,Ana Pabalan,Michael Gombert,Dominic S. Raj
出处
期刊:American Journal of Nephrology
[S. Karger AG]
日期:2024-12-18
卷期号:: 1-23
摘要
Introduction: Understanding the molecular signals associated with the progression of kidney disease is vital for risk stratification and targeted treatment. Recent advances in RNA-sequencing technique has enabled us to characterize extracellular transcriptome profiles for precision diagnostics. Method: We evaluated the plasma mRNA profile of participants exhibiting slow (n=119) and fast (n=119) decline in estimated glomerular filtration rate (eGFR) among the Chronic Renal Insufficiency Cohort (CRIC) in a nested case control study. The two groups were matched for age, sex, race, baseline eGFR, proteinuria and diabetes status. The next generation sequencing data was analyzed using edgeR to identify differentially expressed genes (DEGs) and Ingenuity Pathway Analysis (IPA) was done to identify the associated pathways. We also compared the top plasma DEGs with gene expression in microdissected human CKD kidney. Results: We identified fragments from ~28,000 annotated genes, of which 783 transcripts exhibited differential expression between slow and fast CKD progressors. Among 629 protein coding genes, 469 were overexpressed in slow progressors, while 157 showed increased expression in fast progressors. Expression of GLI2, CUX1, NOTCH1 and LRP1 transcripts were amplified in slow progressors. Pathway analysis linked these differentially expressed genes to WNT/β-catenin signaling, IL-12 signaling and production in macrophages, Netrin-1 Signaling and Epithelial-Mesenchymal Transition pathways. Many of the plasma differentially expressed genes were also upregulated in microdissected human CKD kidney. Conclusion: Warranting further validation, circulating levels of aberrantly expressed transcripts hold potential to be used as biomarkers for fast CKD progression.
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