Semaglutide Enhances Cellular Regeneration in Skin and Retinal Cells In Vitro.

Area of Science:

• Cell Biology
• Pharmacology
• Biochemistry

Background:

• Glucagon-like peptide-1 (GLP-1) is an endogenous hormone with widespread receptor expression.
• GLP-1 receptor agonists (GLP-1RAs) are primarily used for diabetes but exhibit anti-inflammatory and antioxidant properties.
• Semaglutide, a GLP-1RA, is investigated for its protective effects against oxidative stress and its role in wound healing.

Purpose of the Study:

• To explore the protective effects of semaglutide against oxidative stress in human dermal fibroblasts and retinal endothelial cells.
• To assess semaglutide's impact on wound healing in dermal fibroblasts.
• To evaluate semaglutide's cytoprotective mechanisms, including antioxidant and anti-apoptotic actions.

Main Methods:

• Human dermal fibroblasts and retinal endothelial cells were exposed to oxidative stress (H2O2) and treated with varying concentrations of semaglutide.
• Cell viability, ATP levels, apoptosis, and reactive oxygen species (ROS) generation were quantified.
• Wound healing was assessed using scratch assays, and gene expression of antioxidant, ECM, inflammatory, and MMP markers was analyzed via real-time PCR.

Main Results:

• Semaglutide significantly enhanced cell viability and ATP production while reducing apoptosis and ROS levels under oxidative stress.
• The drug markedly accelerated wound closure in fibroblasts, nearing complete restoration.
• Gene expression analysis showed increased antioxidant and extracellular matrix (ECM) genes, and decreased pro-inflammatory cytokines and matrix metalloproteinases (MMPs).

Conclusions:

• Semaglutide exhibits potent antioxidative and cytoprotective effects on dermal fibroblasts and retinal endothelial cells, thereby promoting wound healing.
• These findings underscore the therapeutic potential of semaglutide for managing diabetic foot ulcers and diabetic retinopathy.
• Further in vivo studies are warranted to validate these promising outcomes.