Keratinocytes of the Upper Epidermis and Isthmus of Hair Follicles Express Hemoglobin mRNA and Protein.

The epidermis, the keratinized stratified squamous epithelium surrounding the body surface, offers a valuable framework to investigate how terrestrial animals overcome environmental stresses. However, the mechanisms underlying epidermal barrier function remain nebulous. In this study, we examined genes highly expressed in the human and mouse upper epidermis, the outer frontier that induces various barrier-related genes. Transcriptome analysis revealed that the messenger RNA level of hemoglobin α (HBA), an oxygen carrier in erythroid cells, was enriched in the upper epidermis compared with that in the whole epidermis. Immunostaining analysis confirmed HBA protein expression in human and mouse keratinocytes (KCs) of the stratum spinosum and stratum granulosum. HBA was also expressed in hair follicle KCs in the isthmus region; its expression levels were more prominent than those in interfollicular KCs. HBA expression was not observed in noncutaneous keratinized stratified squamous epithelia of mice, for example, the vagina, esophagus, and forestomach. HBA expression was upregulated in human epidermal KC cultures after UV irradiation, a major cause of skin-specific oxidative stress. Furthermore, HBA knockdown increased UV-induced production of ROS in primary KCs. Our findings suggest that epidermal HBA expression is induced by oxidative stress and acts as an antioxidant, contributing to skin barrier function.