AT2R Activation Improves Wound Healing in a Preclinical Mouse Model

Area of Science:

• Dermatology
• Wound Healing Research
• Molecular Biology

Background:

• Abnormal skin healing leads to chronic wounds and hypertrophic scarring, posing a significant healthcare challenge.
• The antifibrotic angiotensin II type 2 receptor (AT2R) signaling pathway's role in cutaneous wound healing requires further elucidation.

Purpose of the Study:

• To investigate the impact of modulating the AT2R signaling pathway on cutaneous wound healing processes.
• To evaluate the effects of a selective AT2R agonist (C21) and antagonist (PD123319) on wound repair in a murine model.

Main Methods:

• Balb/c mice with full-thickness wounds were topically treated with C21, PD123319, or vehicle.
• Wound healing was assessed on days 7 and 10 post-wounding, including measurements of re-epithelialization, collagen and vascular densities, and cellular infiltration.
• In vitro assays examined the effect of C21 on human fibroblast migration.

Main Results:

• PD123319 and combination treatments accelerated wound re-epithelialization.
• C21 treatment increased collagen and vascular densities and upregulated pro-regenerative genes.
• C21 reduced leukocyte and neutrophil infiltration, while PD123319 increased them, indicating differential immune modulation.

Conclusions:

• AT2R activation with C21 promotes accelerated wound maturation with improved structural and cellular profiles resembling unwounded skin.
• Modulating AT2R signaling represents a potential therapeutic strategy for enhancing skin wound healing and improving tissue quality.
• Targeting AT2R offers a novel approach to manage chronic wounds and reduce scarring.