Wound Healing Effects of Polyethylene Glycol Loxenatide via PI3K/AKT Pathway: In Vitro Evaluation in Human Keratinocytes

J Diabetes Res. 2026;2026(1):e6683809. doi: 10.1155/jdr/6683809.

ABSTRACT

AIM: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) hold clinical promise in promoting wound healing. This study investigated the pro-healing effect and potential molecular mechanism of polyethylene glycol loxenatide (PEG-Lox).

MATERIALS AND METHODS: HaCaT cells were incubated in high glucose (HG) condition with or without PEG-Lox. Cell proliferation and viability were assessed by Cell Counting Kit 8 (CCK8) assay and PI staining. Cell migration was evaluated via Transwell and scratch wound healing assays. Transcriptomic analysis was conducted to identify the potential differentially expressed genes (DEGs). Western blotting was performed to validate protein expression levels of identified DEGs.

RESULTS: Cell proliferation and viability were significantly improved in the PEG-Lox-treated group when compared with the control group. Transwell assay showed that HG inhibited the migration of HaCaT cells, whereas PEG-Lox treatment markedly resulted in a 1.7-fold increase in the number of migrating cells (p < 0.0001). The scratch closure rate was 32.83% after PEG-Lox intervention, which was higher than that in the control group (24.42%, p < 0.001). Transcriptomic analysis found early growth response factor 1 (EGR1) to be the key DEG under PEG-Lox treatment. The inhibition of PI3K/AKT signaling pathway by LY294002 down-regulated the expression of EGR1 and impaired the proliferation and migration of HaCaT cells.

CONCLUSIONS: Our study suggested that GLP-1RA PEG-Lox could promote wound healing by activating the PI3K/AKT/EGR1 signaling pathway, which further uncovered the potential pro-healing effect of GLP-1RAs in wounds.

PMID:42017759 | DOI:10.1155/jdr/6683809