As epidermal keratinocytes differentiate toward the external environment, they express protective genes against foreign insults such as ultraviolet (UV) irradiation, a major cause of oxidative stress in the skin. Oxidative stress is an imbalance between reactive oxygen species and antioxidants, leading to various pathophysiological conditions including skin cancers. To identify novel epidermal genes with UV-protective function expressed in the upper epidermis, we performed a comparative microarray analysis of gene expression between the whole and upper epidermis separated from healthy human skins. It revealed that the mRNA level of hemoglobin α (HBA), which serves as an oxygen transporter in erythroid cells and an antioxidant in some non-erythroid cells, was significantly higher in the upper epidermis. Immunostaining analysis of human and mouse epidermis confirmed that HBA protein was expressed in keratinocytes of the differentiated layers (stratum spinosum and stratum granulosum). Furthermore, human and mouse epidermal keratinocytes showed that HBA expression was more prominent in the bulge region and its upper portion of the hair follicle than in the interfollicular epidermis. We also found that HBA mRNA expression was upregulated in human primary keratinocytes after UV exposure and in the epidermis of UV-induced skin carcinogenesis mouse model from re-analysis of published transcriptome datasets. In contrast, HBA protein expression was not observed in the other stratified squamous epithelia, such as the tongue, esophagus, forestomach, and vagina in mice. Our findings suggest that HBA is a UV-responsive gene in the epidermis, i.e., sun-exposed epithelium, and acts as an endogenous antioxidant, especially for the hair follicle stem cells in the bulge region.

ESDR532 - Unexpected expression of hemoglobin α as an endogenous antioxidant in epidermal keratinocytes

The scientific meeting of the European Society for Dermatological Research (ESDR) is held yearly, usually in September. With an international attendance of more than 1000 skin scientists from around the globe, the four-day event includes short oral presentations from peer-reviewed abstracts, keynote lectures from international experts, sponsored symposia, satellite programs, educational events as well as an important focus on posters, networking and building collaborations amongst scientists. For more information about this year’s meeting visit our website.