Impact of epidermal desquamation on tissue stores of iron.

Background: Although several billion corneocytes are shed from human skin daily, metabolic studies from 50 years ago led to the conclusion that corneocyte desquamation had no measurable impact on systemic protein or iron status in humans.

Objective: To measure iron content of internal organs after introducing local genetic changes in epidermis that alter iron metabolism in skin.

Methods: Iron was measured in tissues and blood from groups of animals 7 weeks after weaning in three different mouse models expressing a transgene in epidermis: a hyperproliferation model in which the HPV16 E7 gene causes a 3-fold increase in epidermal turnover; an epidermal iron sink model in which overexpression of the transferrin receptor causes a 3-4 fold increase of iron in epidermis; a systemic hemochromatosis knockout model that has been crossed with the epidermal iron sink model.

Results: In the hemochromatosis model with the iron sink transgene in epidermis, there was a statistically significant reduction in non-heme iron in serum and in the liver and kidney. In all models there was a statistically significant reduction in non-heme iron in the kidney.

Conclusion: Local changes in iron metabolism in epidermis can have a measurable impact on systemic iron metabolism. By implication, disruptions in epidermal homeostasis might affect systemic levels of trace nutrients, and circulating toxins might be remediated by sequestering them in epidermis.