Integrated analysis of ATAC-seq and RNA-seq reveals ADSCP2 regulates oxidative phosphorylation pathway in hypertrophic scar fibroblasts.

Summary

Using integrated ATAC-seq and RNA-seq, the study shows that ADSCP2 reshapes chromatin accessibility and gene expression in hypertrophic scar fibroblasts, suppressing OXPHOS genes (COX6B1, NDUFA1). Reduced ATP and lactate suggest metabolic reprogramming as a mechanism for anti-fibrotic activity.

Key Findings

• ATAC-seq identified 7,805 differential peaks linked to 3,176 genes; RNA-seq found 345 upregulated and 399 downregulated transcripts after ADSCP2 treatment.
• KEGG enrichment pointed to OXPHOS regulation; COX6B1 and NDUFA1 were significantly downregulated with promoter regions showing increased closure.
• ADSCP2 reduced cellular ATP and lactic acid levels, indicating a shift in cellular energetics.

Clinical Implications

Supports development of peptide-based anti-scar interventions targeting mitochondrial pathways; may guide biomarker-driven dosing and patient selection.

Limitations

• In vitro fibroblast model without in vivo scar validation
• Sample sizes and replicates are not detailed; lack of functional scar outcomes

Future Directions

Evaluate ADSCP2 efficacy and safety in animal models of hypertrophic scarring, develop delivery systems, and map upstream regulators and downstream effectors of OXPHOS modulation.