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

**Authors:** Ayse Ak, Zehra Seda Halbutogullari, Ahu Soyocak, Ebru Onem, Rustu Tastan, Yusufhan Yazir

PMC · DOI: 10.1021/acsomega.5c10013 · ACS Omega · 2025-12-19

## TL;DR

COG133, a peptide mimicking ApoE, shows promise in improving diabetic wound healing by reducing inflammation and fighting bacteria.

## Contribution

The study explores COG133's novel effects on diabetic fibroblasts and its antibacterial activity, suggesting therapeutic potential.

## Key findings

- COG133 enhanced fibroblast migration and upregulated miR-146a while reducing IL-6 and ApoE expression.
- COG133 exhibited antibacterial activity, with notable effects against Chromobacterium violaceum and Pseudomonas aeruginosa biofilms.

## Abstract

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 Chromobacterium
violaceum, and a 55% reduction in Pseudomonas
aeruginosa 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.

## Linked entities

- **Genes:** APOE (apolipoprotein E) [NCBI Gene 348], MIR146A (microRNA 146a) [NCBI Gene 406938], NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790], TRAF6 (TNF receptor associated factor 6) [NCBI Gene 7189], IL6 (interleukin 6) [NCBI Gene 3569]
- **Chemicals:** COG133 (PubChem CID 146159074)
- **Diseases:** diabetes (MONDO:0005015)
- **Species:** Chromobacterium violaceum (taxon 536), Pseudomonas aeruginosa PAO1 (taxon 208964)

## Full-text entities

- **Genes:** NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, TRAF6 (TNF receptor associated factor 6) [NCBI Gene 7189] {aka MGC:3310, RNF85}, MIR146A (microRNA 146a) [NCBI Gene 406938] {aka MIRN146, MIRN146A, miR-146a, miRNA146A}, APOE (apolipoprotein E) [NCBI Gene 348] {aka AD2, APO-E, ApoE4, LDLCQ5, LPG}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}
- **Diseases:** Diabetic (MESH:D003920), inflammation (MESH:D007249)
- **Chemicals:** COG133 (-)
- **Species:** Chromobacterium violaceum (species) [taxon 536], Pseudomonas aeruginosa PAO1 (strain) [taxon 208964], Homo sapiens (human, species) [taxon 9606], Bacteria Latreille et al. 1825 (Bacteria stick insect, genus) [taxon 629395]

## Full text

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## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12809331/full.md

## References

46 references — full list in the complete paper: https://tomesphere.com/paper/PMC12809331/full.md

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Source: https://tomesphere.com/paper/PMC12809331