Comparative Analysis of Oral and Skin Keratinocytes Responses to Oxidative Stress

Oxidative stress caused by excessive reactive oxygen species (ROS) disrupts skin and oral epithelial homeostasis and contributes to skin aging, inflammation, periodontitis, and mucosal injury. As the principal defenders in both tissues, keratinocytes may exhibit divergent responses to oxidative stress. However, most existing studies have examined skin or oral keratinocytes in isolation, with few comparative investigations of their tolerance, repair capacity, and antioxidant mechanisms under oxidative stress. In this study, we systematically compared immortalized oral keratinocytes (TIGK) and skin keratinocytes (HaCaT) under hydrogen peroxide (H₂O₂)–induced oxidative stress. Functional analyses, including cell survival, ROS accumulation, wound healing, and proliferation recovery assays, were combined with transcriptomic profiling to evaluate differences in antioxidant and pro-oxidant systems. TIGK exhibited significantly higher survival rates, lower ROS accumulation, and superior migratory and proliferative recovery compared with HaCaT after oxidative insult. Transcriptomic analysis further revealed that TIGK consistently expressed higher levels of antioxidant genes and enzymes. In contrast, HaCaT showed greater ROS accumulation and relatively limited antioxidant defenses. Oral and skin keratinocytes adopt distinct adaptive mechanisms under oxidative stress. The intrinsic redox advantage of oral keratinocytes provides new insights into their rapid wound-healing capacity and may inform strategies to enhance epithelial resilience.