DUSP1 deficiency accelerates UVB‑induced HDF cell senescence by regulating ferroptosis.

Abstract

Ultraviolet (UV) radiation is a major factor contributing to skin aging. Ferroptosis, a recently identified form of regulated cell death, remains controversial in its role in mid‑wave ultraviolet (UVB)‑induced skin photoaging. Preliminary evidence suggests that Dual‑Specificity Phosphatase 1 (DUSP1) may be associated with both skin photoaging and ferroptosis. This study aims to investigate the role of ferroptosis and the regulatory mechanism of DUSP1 in a UVB‑induced stress‑induced premature senescence (UVB‑SIPS) model of human dermal fibroblasts (HDFs). Our findings demonstrate that ferroptosis occurs in HDFs following UVB irradiation. Treatment with a low concentration (0.5 µM) of the ferroptosis inhibitor ferrostatin‑1 (Fer‑1) alleviated UVB‑induced senescence, reduced intracellular reactive oxygen species (ROS) accumulation, and promoted the expression of type I and type III collagen. We also observed a decrease in DUSP1 protein expression in HDFs after UVB exposure. Furthermore, in vitro knockdown of DUSP1 exacerbated cellular senescence, impaired proliferative capacity, intensified cell‑cycle arrest, upregulated the expression of senescence‑associated proteins (p53, p21, p16), and reduced the production of type I and type III collagen. Subsequent experiments indicated that DUSP1 knockdown may promote ferroptosis by down‑regulating the SLC7A11/GPX4 axis, thereby accelerating UVB‑induced photoaging in HDFs. These results suggest that DUSP1 might serve as a novel therapeutic target for mitigating skin photoaging.