The prevalence of chronic kidney disease (CKD) is gradually rising worldwide. Patients often remain asymptomatic for an extended period, leaving them unaware of their condition, which can lead to progressing to end-stage renal disease and cause significant economic burden. Improved understanding of CKD pathogenesis can enhance early detection and facilitate advances in drug development. Here, we performed proteomic and phosphoproteomic analyses of the mouse unilateral ureteral obstruction model to explore the molecular mechanisms of chronic kidney injury. 474 significantly differentially expressed proteins and 96 significantly differentially expressed phosphoproteins were screened, respectively. Chronic kidney injury involves complex metabolic pathways such as citrate cycle and hematopoietic system in proteome, and mitochondrial oxidative phosphorylation suppression is a notable alteration. The phosphoproteomic analysis revealed a significant upregulation in epithelial mesenchymal transition and P53 pathways, with a corresponding increase in the phosphorylation of Jun at serine 73. Utilizing HK2 cells, we observed that the reduction oxidative phosphorylation was consistently associated with an augmentation in oxidative stress, which subsequently activated Jun and induced apoptosis. Proteins that act as hubs in these pathways may be candidate targets for CKD intervention. These findings contribute significantly to the current understanding of CKD and provide valuable insights for future studies. SIGNIFICANCE: Chronic kidney disease (CKD) incidence rising annually with varied etiologies, kidney often irreversibly fibrotic, the treatment options are limited and often ineffective due to deficient understanding of renal fibrosis mechanisms. Despite the extensive efforts and numerous omics studies conducted on renal fibrosis, to date, no study has been undertaken to investigate the role of phosphorylated proteins in UUO models. Previously, we performed a comprehensive transcriptome and proteome analysis based on the CKD model, but the potential alterations in the phosphoproteome were not addressed. Here, an integrated proteomic and phosphoproteomic landscape of CKD was completed, which was the the first phosphoproteomic profiles of UUO model. Phosphoproteomic profile suggests that the epithelial mesenchymal transition and P53 pathways is significantly activated in mouse models of kidney injury, and the core protein Jun played a key role in CKD. And a preliminary correlation between P-Jun and oxidative phosphorylation was found base on HK2 cells. Our work contributes to a deeper understanding of the disease characteristics and molecular mechanisms of CKD. Identifying potential CKD targets from proteome and phosphoproteome may provide valuable insights for early diagnosis and treatment of CKD.

Linxiao Sun

Cheng Wang

Zhongjing Zhou

Qiangqiang Li

Journal of Proteomics

蛋白质组学杂志面向蛋白质组学、生物标志物发现、蛋白质分析、植物蛋白质组学、微生物和动物蛋白质组学、人体研究、质谱组织成像、非常规和非模型生物蛋白质组学领域的蛋白质科学家和分析化学家，和蛋白质生物信息学。该杂志欢迎新领域和即将到来的领域的论文，如代谢组学、基因组学、系统生物学、毒理学组学、药物蛋白质组学。蛋白质组学杂志统一了基础科学家和临床医生，并包括转化研究。欢迎对评论、网络研讨会和主题问题提出建议。

The Journal of Proteomics is a journal dedicated to proteomics, biomarker discovery, protein analysis, plant proteomics, microbiome and animal proteomics, human studies, mass spectrometry imaging, as well as unconventional and non-model organism proteomics. This journal serves protein scientists, analytical chemists, and proteomics bioinformaticians. We welcome research papers from emerging and cutting-edge fields, including metabolomics, genomics, systems biology, toxicology, and drug proteomics. The Journal of Proteomics aims to bridge the gap between basic scientists and clinicians, encompassing translational research. We also welcome suggestions for reviews, webinars, and thematic issues.

《Journal of Proteomics》是一本专注于蛋白质组学、生物标志物发现、蛋白质分析、植物蛋白质组学、微生物和动物蛋白质组学、人体研究、质谱组织成像以及非常规和非模型生物蛋白质组学的期刊。该杂志旨在服务于蛋白质科学家、分析化学家和蛋白质生物信息学家。我们欢迎来自新兴领域和前沿领域的研究论文，包括代谢组学、基因组学、系统生物学、毒理学组学和药物蛋白质组学。《Journal of Proteomics》致力于促进基础科学家与临床医生之间的交流，并涵盖转化研究。我们也欢迎对评论、网络研讨会和主题问题的建议。

Category	Quartile
生物学	2
生物学, 生化研究方法	2

An integrated proteomic and phosphoproteomic landscape of chronic kidney disease

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Journal Info

Category	Quartile
BIOCHEMICAL RESEARCH METHODS	2