Comprehensive Transcriptomic Profiling Reveals Tissue-Specific Molecular Signatures and Dysregulated Pathways in Diabetic Foot Ulcers
Summary:** This study performed RNA sequencing on skin, adipose, and muscle tissues from DFU patients and non-ulcerated diabetic controls to uncover tissue-specific molecular drivers of DFU pathogenesis. Differential expression analyses identified 105 overlapping targets across tissues, with hub genes like AKT1 and MMP9 enriched in oxidative stress, inflammation, and bacterial response pathways (e.g., AGE-RAGE, TNF, IL-17). Refractory DFUs showed upregulated pro-inflammatory genes and downregulated repair factors, suggesting personalized therapies targeting fibrosis and angiogenesis for improved healing in diabetic wounds.
Key Highlights:
- Dataset: Skin/adipose/muscle from 10 DFU patients vs. 10 controls; 105 common DEGs, 10 hubs (AKT1, EGFR, MMP9).
- Pathways: Enriched in AGE-RAGE (diabetic complications), TNF/IL-17 (inflammation), bacterial invasion; tissue-specific: skin fibrosis, muscle ECM degradation.
- Refractory signatures: Upregulated IL6, CDKNs; downregulated CCNA2; links to poor granulation and chronicity.
- Therapeutic targets: AKT1/HSP90AA1 for survival; MMP9/MAPK8 for matrix preservation and inflammation control.
- Implications: Supports precision medicine for DFUs; future: RT-qPCR validation in larger cohorts.
Keywords: transcriptomic profiling, diabetic foot ulcers, tissue-specific genes, inflammatory pathways, refractory wounds