Cornification of epidermal keratinocytes is associated with the breakdown of organelles and other cell components. The degradation of hemoproteins, such as cytochrome c and cytochrome P450 family members, releases heme, a potent source of oxidative stress. Heme oxygenase 1 (HO-1) converts heme into ferrous iron, carbon monoxide and biliverdin, a strong antioxidant. Here, we show by single cell transcriptomics and immunohistochemistry that HO-1 is upregulated during terminal differentiation of human keratinocytes, leading to the accumulation of HO-1 mRNA and protein in the granular layer of the epidermis. For the study of the functions of HO-1 in the epidermis, we crossed Hmox1-floxed and K14-Cre mice to delete HO-1 specifically in keratinocytes. Isolation and in vitro differentiation of keratinocytes from Hmox1f/f K14-Cre mice confirmed lack of HO-1 expression whereas HO-1 was upregulated in keratinocytes isolated from wildtype mice. The genetic inactivation of HO-1 did not impair formation of the stratum corneum and survival of Hmox1f/f K14-Cre mice, suggesting that HO-1 is dispensable for epidermal differentiation under non-stressed conditions. The establishment of epidermal HO-1 knockout mice facilitates the study of redox processes and iron metabolism of the epidermis during stress, infections and aging.

ESDR203 - Constitutive expression of heme oxygenase-1 in differentiated keratinocytes is abolished in a new mouse model for the study of epidermal iron metabolism and redox balance

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.