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Azadeh S S, Keshmiri Neghab H. Analysis of Mitochondrial-Related Proteins in Modulating Wound Healing Pathways: A Network-Based Study. ASWTR 2025; 22 (4) :15-23
URL: http://icml.ir/article-1-698-en.html

Background: Wound healing is a complex, multi-stage process regulated by the interplay of metabolic, inflammatory, and redox signaling pathways. However, the systems-level integration of these mechanisms, particularly the role of mitochondrial function, remains insufficiently understood.
Methods: In this study, an in silico systems biology approach was employed to investigate interactions among ten key regulatory genes (HIF1A, AKT1, MAPK1, MTOR, NFKB1, STAT3, SIRT1, PPARGC1A, NOX4, and PRKAA1). A protein–protein interaction network was constructed using STRING and analyzed in Cytoscape to identify hub genes and functional modules. KEGG pathway enrichment analysis was performed to determine significantly associated biological pathways.
Results: The PPI network revealed a highly interconnected structure with central hub genes including AKT1, MTOR, MAPK1, STAT3, and NFKB1. Enrichment analysis identified key pathways such as HIF-1, PI3K–Akt, MAPK, AMPK, and NF-κB signaling. Mitochondrial regulators (SIRT1, PPARGC1A, PRKAA1) showed strong connectivity with growth and inflammatory pathways, while NOX4-mediated redox signaling was linked to both angiogenesis and immune responses.
Conclusion: These findings demonstrate that wound healing is governed by an integrated regulatory network in which mitochondrial function and redox balance play central roles in coordinating cellular metabolism, inflammation, and tissue regeneration.