Particulate Matter-Induced Skin Injury: A Dual-Pathway AhR-Nrf2 Framework for Epidermal Homeostasis and Therapeutic Targeting.

The aryl hydrocarbon receptor (AhR) is highly expressed in keratinocytes and functions as an environmental sensor regulating xenobiotic metabolism, epidermal differentiation, and inflammatory responses. Particulate matter (PM), a major environmental pollutant containing reactive oxygen species (ROS), transition metals, and polycyclic aromatic hydrocarbons (PAHs), induces oxidative stress and inflammation, leading to skin barrier dysfunction. Transition metals generate ROS via Fenton-type reactions, whereas PAHs undergo AhR-mediated metabolism that further amplifies oxidative stress. Excessive ROS promotes inflammatory cytokine expression and disrupts barrier-related protein expression. In response, activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway induces antioxidant enzymes, including heme oxygenase-1 (HO-1), to counteract oxidative damage. However, sustained PM exposure may overwhelm these defense mechanisms, resulting in impaired cellular homeostasis. Although the roles of AhR and Nrf2 have been extensively investigated individually, their coordinated regulation in PM-induced skin injury remains underexplored. This review summarizes current evidence on the functional interplay between AhR and Nrf2 and discusses how coordinated activation of these pathways integrates xenobiotic metabolism, antioxidant defense, and barrier-associated functions. Overall, the available evidence supports a dual-pathway framework for maintaining epidermal homeostasis under PM-induced environmental stress.