Abstract: SA-PO0870
Systems-Level Analysis Identifies Early Pathogenic Pathways in High-Protein Diet-Induced Kidney Injury
Session Information
- Health Maintenance, Nutrition, and Metabolism
October 24, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Health Maintenance, Nutrition, and Metabolism
- 1500 Health Maintenance, Nutrition, and Metabolism
Authors
- Yoshikawa, Miyu, Tokyo Kagaku Daigaku Daigakin Ishigaku Sogo Kenkyuka, Bunkyo, Tokyo, Japan
- Kikuchi, Hiroaki, Tokyo Kagaku Daigaku Daigakin Ishigaku Sogo Kenkyuka, Bunkyo, Tokyo, Japan
- Tsuboya, Tomohiro, Tokyo Kagaku Daigaku Daigakin Ishigaku Sogo Kenkyuka, Bunkyo, Tokyo, Japan
- Sugimoto, Mari, Tokyo Kagaku Daigaku Daigakin Ishigaku Sogo Kenkyuka, Bunkyo, Tokyo, Japan
- Suzuki, Takefumi, Tokyo Kagaku Daigaku Daigakin Ishigaku Sogo Kenkyuka, Bunkyo, Tokyo, Japan
- Ando, Fumiaki, Tokyo Kagaku Daigaku Daigakin Ishigaku Sogo Kenkyuka, Bunkyo, Tokyo, Japan
- Arai, Yohei, Tokyo Kagaku Daigaku Daigakin Ishigaku Sogo Kenkyuka, Bunkyo, Tokyo, Japan
- Fujiki, Tamami, Tokyo Kagaku Daigaku Daigakin Ishigaku Sogo Kenkyuka, Bunkyo, Tokyo, Japan
- Mandai, Shintaro, Tokyo Kagaku Daigaku Daigakin Ishigaku Sogo Kenkyuka, Bunkyo, Tokyo, Japan
- Mori, Yutaro, Tokyo Kagaku Daigaku Daigakin Ishigaku Sogo Kenkyuka, Bunkyo, Tokyo, Japan
- Mori, Takayasu, Tokyo Kagaku Daigaku Daigakin Ishigaku Sogo Kenkyuka, Bunkyo, Tokyo, Japan
- Susa, Koichiro, Tokyo Kagaku Daigaku Daigakin Ishigaku Sogo Kenkyuka, Bunkyo, Tokyo, Japan
- Sohara, Eisei, Tokyo Kagaku Daigaku Daigakin Ishigaku Sogo Kenkyuka, Bunkyo, Tokyo, Japan
Background
Dietary protein intake influences progression of chronic kidney disease (CKD), yet the molecular mechanisms underlying high-protein diet (HPD)-induced kidney injury remain unclear. Recent multi-omics approaches enable comprehensive characterization of biological responses across transcriptional, proteomic, and metabolic layers. Here, we aimed to identify early molecular alterations induced by HPD using integrated multi-omics analyses and Bayesian data integration to prioritize transcription factors (TFs) potentially involved in renal injury.
Methods
Mice were fed either a normal-protein diet or HPD, and kidneys were collected after 2 and 4 weeks. Whole-kidney samples underwent RNA sequencing and quantitative proteomic analyses, while metabolites were profiled by capillary electrophoresis time-of-flight mass spectrometry (CE-TOF-MS). Bayesian integration analysis was applied across datasets to prioritize 1,344 curated mouse TFs according to their probability of contributing to kidney injury.
Results
RNA-seq at 2 weeks demonstrated induction of metabolic genes involved in gluconeogenesis and energy metabolism, including Pck1, Mogat2, and Slc25a25. Persistent upregulation of Pck1 and Slc25a25 was also observed at 4 weeks. Integrated transcriptomic and proteomic analyses consistently identified sustained induction of PCK1, suggesting metabolic reprogramming in renal tubular cells under HPD conditions.
Metabolomic profiling revealed depletion of tricarboxylic acid (TCA) cycle intermediates, including citrate and isocitrate, together with a reduced ATP/AMP ratio, indicating mitochondrial energetic stress.
Bayesian integration prioritized 11 TFs potentially involved in HPD-associated kidney injury. Among them, Myc, Stat4, Irf7, E2f1, Foxm1, and Ybx1 have previously been implicated in tubular injury and maladaptive repair pathways.
Conclusion
Integrated multi-omics analysis revealed that HPD induces early metabolic reprogramming and mitochondrial energetic stress in the kidney, characterized by persistent activation of PCK1-associated pathways. Bayesian data integration identified candidate TF networks potentially driving HPD-induced renal injury, including regulators associated with proliferative stress and maladaptive tubular repair.These findings suggest that targeting these signaling pathways may represent a novel therapeutic strategy for preventing CKD progression induced by HPD.