OBP2A regulates epidermal barrier function and protects against cytotoxic small hydrophobic molecules

The skin is constantly exposed to environmental sensory stimuli, which may include harmful volatiles and small hydrophobic molecules. However, the skin's protective mechanism against the latter agents is unclear. Here, we demonstrate that odorant binding protein 2A (OBP2A) protects epidermal keratinocytes against cytotoxic small hydrophobic molecules. OBP2A is mainly expressed in human epidermal keratinocytes. Cellular resistance to cytotoxic aldehyde and lipids was reduced in keratinocytes when OBP2A was silenced. Furthermore, silencing of OBP2A in a three-dimensional epidermal equivalent model resulted in impairment of epidermal barrier function. Inhibition of OBP2A caused disruption of keratinocyte lipid metabolism and induced endoplasmic reticulum stress. OBP2A expression was markedly decreased in the epidermis of atopic dermatitis lesional skin. In addition, interleukin-13 suppressed the expression of OBP2A in keratinocytes. Overall, our findings suggest that OBP2A regulates epidermal barrier function and contributes to protection of the skin against harmful small hydrophobic molecules.