Therapeutic Potential of the ApoE-Mimicked Peptide COG133: Regulation of miRNA146-a in Diabetic Fibroblasts and Antibacterial Activity

COG133, an apolipoprotein E-derived mimetic peptide, has been proposed as a therapeutic candidate due to its immunomodulatory properties. Its potential role in diabetic wound healing, where impaired fibroblast function and chronic inflammation are major obstacles, remains largely unexplored. In this study, human diabetic dermal fibroblasts were treated with COG133 to evaluate its effects on cell viability, migration, and gene expression of ApoE, miR-146a, NF-κB, TRAF-6, and IL-6. In addition, the antibacterial and antibiofilm activities of COG133 were assessed against Gram-positive and Gram-negative bacteria. COG133 enhanced fibroblast migration without affecting viability, upregulated miR-146a, and reduced IL-6 and ApoE expression, while NF-κB and TRAF-6 remained unchanged. Antibacterial assays revealed inhibitory effects, with the lowest MIC against <i>Chromobacterium violaceum</i>, and a 55% reduction in <i>Pseudomonas aeruginosa</i> PAO1 biofilm formation. These results suggest that COG133 modulates inflammatory signaling and exhibits antibacterial properties, highlighting its therapeutic potential in supporting wound healing in diabetes.