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July 4, 2025Journal of Translational MedicineOpen Access

Uncovering key markers and therapeutic targets for renal fibrosis in diabetic kidney disease through bulk and single-cell RNA sequencing

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Authors

LLLijuan LiTMTao MiXGXueyun Gao

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Overview

Translational transcriptomic analysis reveals PROM1 and THY1 as divergent regulators of renal fibrosis in diabetic kidney disease, highlighting novel diagnostic and therapeutic targets.

Key Points

  • To identify key diagnostic biomarkers and actionable therapeutic targets involved in tubulointerstitial renal fibrosis in diabetic kidney disease.
  • Analyzed bulk and single-cell RNA sequencing datasets using weighted gene co-expression network analysis (WGCNA) and machine learning to build a ssGSEA-based FibrosisScore model.
  • Screened small-molecule modulators from the ZINC chemical database using molecular docking.
  • Evaluated candidate gene expression in a streptozotocin (STZ)-induced diabetic mouse model and clinical datasets from Nephroseq V5.
  • The FibrosisScore model demonstrated robust predictive accuracy across training and validation cohorts, achieving AUCs of 0.803, 0.992, and 0.891.
  • PROM1 (enriched in proximal tubule cells) and THY1 (enriched in fibroblasts) each exhibited diagnostic AUCs > 0.9; PROM1 promoted fibrosis, while THY1 exerted protective, antifibrotic effects in STZ mice.
  • Virtual screening and molecular docking identified two candidate therapeutic small molecules, ZINC402830 and ZINC3830400.

Cite This Study

Li et al. (2025) studied this question.

synapsesocial.com/papers/6a8d58dbc35d840b0ddcd5e4https://doi.org/10.1186/s12967-025-06554-8
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