Deficiency of NF-Erythroid 2-Related Factor 2 Exacerbates the Scar Through ERK Signaling Pathway

Scar, primarily composed of poorly structured and disordered collagen, is mainly characterized by excessive fibroblast activation and abnormal collagen deposition. Previous studies have shown that fibroblast activation is closely related to the imbalance of inflammatory responses and reactive oxygen species. NF-erythroid 2-related factor 2 (Nrf2) is an important transcription factor involved in regulating inflammation and oxidative stress. Although current evidence suggests that Nrf2 influences the occurrence of skin fibrosis, the role of Nrf2 in scar formation remains unknown.

In this study, we used qRT-PCR, Western Blot, and Immunohistochemical/Immunofluorescent staining to explore the role of Nrf2 in wound healing and scar formation.

The deficiency of Nrf2 delayed the process of wound healing and exacerbated collagen deposition. Moreover, significant elevations in the mRNA expression of collagen synthesis-related genes were observed in Nrf2-deficient mice in vivo and in vitro. Meanwhile, Nrf2 deficiency also exacerbated inflammatory responses, leading to abnormal fibroblast activation and sustained activation of the ERK signaling pathway.

These results suggest that Nrf2 plays a crucial role in fibroblast activation and scar formation, and our findings offer a novel therapeutic approach for reducing scar formation after skin injury.