Distinct Molecular Relationships and Partial Pathway Convergence of Anserine and RRR-α-Tocopherol in Human Diabetic Kidney Disease
- 1Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia
- 2Center of Artificial Intelligence for Precision Medicines, King Abdulaziz University, Jeddah 21589, Saudi Arabia
- 3Vascular Biology Research Unit, King Fahad Medical Research Center, King Abdulaziz University, Jeddah 21589, Saudi Arabia
Abstract
Diabetic kidney disease (DKD) involves interacting metabolic, inflammatory, vascular, and fibrotic disturbances. This study investigated the molecular relationships of anserine and RRR-α-tocopherol with human DKD using a disease-centered computational framework in which compound–target evidence was established independently before integration with kidney transcriptomic data. Stage-associated transcription was analyzed in 36 human kidney samples spanning Control, Early DKD, and Advanced DKD, with external assessment in two independent cohorts, followed by evidence-based prioritization, pathway analysis, renal single-cell localization, and sensitivity analyses. Predefined target sets comprised 100 anserine and 111 RRR-α-tocopherol targets, with only 16 shared. Integration yielded 21 prioritized compound–DKD relationships involving 20 unique genes. Despite limited target overlap, the primary pathway analysis identified shared enrichment in Class A G protein-coupled receptor, Gαi, interleukin, and receptor tyrosine kinase signaling; only receptor tyrosine kinase signaling remained shared under conservative target-confidence restriction. The 20 genes localized across diverse tubular, immune, vascular, and stromal populations. Sensitivity analyses retained 17 of 21 relationships under stricter target-confidence criteria and showed external gene–DKD replication for 18 of 21 relationships in at least one cohort. These findings define a transparent, hypothesis-generating framework for experimental testing without implying therapeutic efficacy or a confirmed mechanism of action.
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BibTeX
@article{mosaoa2026distinct,
title = {{Distinct Molecular Relationships and Partial Pathway Convergence of Anserine and RRR-α-Tocopherol in Human Diabetic Kidney Disease}},
author = {Rami M. Mosaoa},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27209279},
url = {https://www.mdpi.com/1422-0067/27/20/9279},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Distinct Molecular Relationships and Partial Pathway Convergence of Anserine and RRR-α-Tocopherol in Human Diabetic Kidney Disease
AU - Rami M. Mosaoa
PY - 2026
DA - 2026/10/01
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27209279
UR - https://www.mdpi.com/1422-0067/27/20/9279
AB - Diabetic kidney disease (DKD) involves interacting metabolic, inflammatory, vascular, and fibrotic disturbances. This study investigated the molecular relationships of anserine and RRR-α-tocopherol with human DKD using a disease-centered computational framework in which compound–target evidence was established independently before integration with kidney transcriptomic data. Stage-associated transcription was analyzed in 36 human kidney samples spanning Control, Early DKD, and Advanced DKD, with external assessment in two independent cohorts, followed by evidence-based prioritization, pathway analysis, renal single-cell localization, and sensitivity analyses. Predefined target sets comprised 100 anserine and 111 RRR-α-tocopherol targets, with only 16 shared. Integration yielded 21 prioritized compound–DKD relationships involving 20 unique genes. Despite limited target overlap, the primary pathway analysis identified shared enrichment in Class A G protein-coupled receptor, Gαi, interleukin, and receptor tyrosine kinase signaling; only receptor tyrosine kinase signaling remained shared under conservative target-confidence restriction. The 20 genes localized across diverse tubular, immune, vascular, and stromal populations. Sensitivity analyses retained 17 of 21 relationships under stricter target-confidence criteria and showed external gene–DKD replication for 18 of 21 relationships in at least one cohort. These findings define a transparent, hypothesis-generating framework for experimental testing without implying therapeutic efficacy or a confirmed mechanism of action.
SN - 1422-0067
ER -