Integrated Single-Cell Transcriptome and eQTL Analyses Reveal the Role of PZP in Aging and Chronic Kidney Disease

IF 3.2 4区医学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Journal of Gene Medicine Pub Date : 2025-03-09 DOI:10.1002/jgm.70015

Xinhui Huang, Cheng Zhu, Shiqi Lv, Yulin Wang, Jiayi Wang, Shuangxin Yuan, Yue Yang, Xiaoqiang Ding, Xiaoyan Zhang

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引用次数: 0

Abstract

Background

Aging is a known driver of chronic kidney disease (CKD), yet the genetic mechanisms linking these two conditions remain unclear. This study aims to explore the role of CD8+ central memory T (T_CM) cells and their associated gene expression in the interaction between aging and CKD.

Methods

Peripheral blood samples from young controls, elderly individuals, and CKD patients were analyzed using single-cell RNA sequencing to investigate immune cell populations. Expression quantitative trait loci (eQTL) and Mendelian randomization analyses were performed using data from genomic cohorts, including the UK Biobank and FinnGen, to assess causal relationships. Experimental validation evaluated correlations between pregnancy zone protein (PZP) expression and clinical indicators such as age, glomerular filtration rate (GFR), serum creatinine, and proteinuria.

Results

Increased proportions of CD8+ T_CM cells were observed in elderly individuals and CKD patients. PZP was identified as a key genetic factor in CKD progression and aging, linked to metabolic reprogramming and impaired intercellular communication. PZP expression correlated significantly with aging (r = 0.818, p = 0.047), reduced GFR (r = −0.557, p = 0.011), elevated serum creatinine (r = 0.507, p = 0.019), and proteinuria (r = 0.761, p = 0.047).

Conclusions

Shared genetic and immunological mechanisms link CKD and aging, with CD8+ T_CM cells contributing to immune dysregulation and chronic inflammation. The dual role of PZP, involving its upregulation, disrupted immune communication, and metabolic reprogramming, highlights its potential as a biomarker and therapeutic target for aging-associated kidney diseases.

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来源期刊

Journal of Gene Medicine 医学-生物工程与应用微生物

CiteScore

6.40

自引率

0.00%

发文量

审稿时长

6-12 weeks

期刊介绍： The aims and scope of The Journal of Gene Medicine include cutting-edge science of gene transfer and its applications in gene and cell therapy, genome editing with precision nucleases, epigenetic modifications of host genome by small molecules, siRNA, microRNA and other noncoding RNAs as therapeutic gene-modulating agents or targets, biomarkers for precision medicine, and gene-based prognostic/diagnostic studies. Key areas of interest are the design of novel synthetic and viral vectors, novel therapeutic nucleic acids such as mRNA, modified microRNAs and siRNAs, antagomirs, aptamers, antisense and exon-skipping agents, refined genome editing tools using nucleic acid /protein combinations, physically or biologically targeted delivery and gene modulation, ex vivo or in vivo pharmacological studies including animal models, and human clinical trials. Papers presenting research into the mechanisms underlying transfer and action of gene medicines, the application of the new technologies for stem cell modification or nucleic acid based vaccines, the identification of new genetic or epigenetic variations as biomarkers to direct precision medicine, and the preclinical/clinical development of gene/expression signatures indicative of diagnosis or predictive of prognosis are also encouraged.