Dionata Araújo de Oliveira¹, Laís Lacerda Brasil de Oliveira¹, Sheheryar¹, Ivna de Lima Ferreira Gomes¹, Fernanda Soares Macedo¹, Felipe Augusto Rocha Rodrigues¹, Edmar Maciel Lima Júnior¹, Manoel Odorico de Moraes Filho¹, Carlos Roberto Koscky Paier¹, Maria Elisabete Amaral de Moraes¹

Biological dressings made from fish skin have become promising options for wound care because of their compatibility with the body and ability to speed up healing. In this study, we examined the proteomic response in mouse full-thickness skin wounds treated with Oreochromis niloticus (tilapia) skin, alongside positive and negative controls. Skin samples were collected for label-free proteomic analysis and the protein extracts were then reduced with dithiothreitol, alkylated with iodoacetamide and trypsinized, desalinated and finally analyzed by QExactive™ UHMR Hybrid Quadrupole-Orbitrap™ liquid chromatograph coupled mass spectrometer (LC-MS). Raw files were processed in MaxQuant for protein identification and quantification, analyzed in Perseus for filtering, normalization and statistics, and in MetaboAnalyst for visualization and multivariate analysis. Hierarchical clustering identified 25 highly abundant proteins that differentiated the treatment groups. Principal component analysis (PCA) showed clear separation between groups, with the group treated with tilapia skin presenting a distinct proteomic profile from controls. The greater dispersion of samples from this group suggests variability in response to treatment, while controls showed greater uniformity. The tilapia skin group displayed a unique proteomic signature, characterized by increased levels of proteins involved in extracellular matrix (ECM) remodeling, immune response, and cell migration. Notably, Q7TMH9 (Krt6a), AOA0G4MY62 (S100A9), and AOA1Q0STI3 (H2-Ab1) were elevated, hinting at improved epithelial regeneration and a regulated immune response. AOA1W2PQH3 (FAM173B) showed reduced levels in the group treated with tilapia skin, which may indicate less oxidative stress or mitochondrial dysfunction, favoring a more stable environment for tissue repair and potentially less chronic pain. Conversely proteins like P47694 (Gstm1) and P63092 (Tpi1) were reduced, suggesting decreased oxidative stress and glycolytic activity. These results support the potential of tilapia skin to promote a healing-friendly wound environment by influencing key molecular pathways.

Agradecimentos: The authors would like to thank Analytical Laboratory and Bioterium of Drug Research and Development Center (NPDM) of Federal University of Ceara (UFC). This study was financed in part by the National Council for Scientific and Technological Development (CNPQ).