Wnt/β-Catenin Signaling Pathway Is Involved in Phenotypic Transformation of Human Skin Fibroblasts Induced by IL-17A

Hypertrophic scar (HTS) formation following severe trauma or burns remains a significant clinical challenge due to the lack of effective treatments, imposing substantial psychological burdens. Chronic inflammation is a key driver of HTS pathogenesis. Interleukin-17A (IL-17A), a critical inflammatory cytokine implicated in organ fibrosis, may play a role in HTS formation, but its function and mechanism in cutaneous scarring are not well defined.

We collected 10 pairs of HTSs and normal skin tissues from patients with burns and examined the expression of IL-17A and Wnt signaling pathway-related molecules by immunohistochemistry and Western blot. These findings were further verified in rabbit ear scar experiments.

IL-17A protein expression was significantly higher in HTSs than in normal skin, whereas Wnt signaling pathway-related molecules were downregulated in the HTS group. In rabbit ear scar models, Wnt signaling inhibitors aggravated HTS development, whereas activators partially inhibited HTS formation.

Our findings demonstrate that IL-17A may target cyclin D1 downstream of the Wnt/β-catenin signaling pathway. These findings represent a promising therapeutic target for the prevention and treatment of HTSs.