Discovery of hemoglobin in the epidermis sheds new light on our skin's protective properties

Researchers have shown for the first time that hemoglobin, a protein found in red blood cells, where it binds oxygen, is also present in the epidermis, our skin's outermost body tissue. The study(opens in new tab/window), which appears in the Journal of Investigative Dermatology(opens in new tab/window), published by Elsevier, provides important insights into the properties of our skin's protective external layer.

This research was driven by a curiosity about how the epidermis protects our delicate body from the environment and what unexpected molecules are expressed in the epidermis. Researchers discovered the hemoglobin α protein in keratinocytes of the epidermis and in hair follicles. This unexpected evidence adds a new facet to the understanding of the workings of our skin's defense mechanisms.

Lead investigator of the study Masayuki Amagai, MD, PhD, Department of Dermatology, Keio University School of Medicine, Tokyo, and Laboratory for Skin Homeostasis, RIKEN Center for Integrative Medical Sciences, Yokohama, explains: "The epidermis consists of keratinized stratified squamous epithelium, which is primarily composed of keratinocytes. Previous studies have identified the expression of various genes with protective functions in keratinocytes during their differentiation and formation of the outer skin barrier. However, other barrier-related genes escaped prior detection because of difficulties obtaining adequate amounts of isolated terminally differentiated keratinocytes for transcriptome analysis."

Hemoglobin binds gases such as oxygen, carbon dioxide, and nitric oxide, and it is an iron carrier via the heme complex. These properties make epidermal hemoglobin a prime candidate for antioxidant activity and potentially other roles in barrier function.

Professor Amagai continues: "We conducted a comparative transcriptome analysis of the whole and upper epidermis, both of which were enzymatically separated as cell sheets from human and mouse skin. We discovered that the genes responsible for producing hemoglobin were highly active in the upper part of the epidermis. To confirm our findings, we used immunostaining to visualize the presence of hemoglobin α protein in keratinocytes of the upper epidermis."

Professor Amagai concludes: "Our study showed that epidermal hemoglobin was upregulated by oxidative stress and inhibited the production of reactive oxygen species in human keratinocyte cell cultures. Our findings suggest that hemoglobin α protects keratinocytes from oxidative stress derived from external or internal sources such as UV irradiation and impaired mitochondrial function, respectively. Therefore, the expression of hemoglobin by keratinocytes represents an endogenous defense mechanism against skin aging and skin cancer."

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Notes for editors

The article is “Keratinocytes of the Upper Epidermis and Isthmus of Hair Follicles Express Hemoglobin mRNA and Protein,” by Umi Tahara, Takeshi Matsui, Toru Atsugi, Keitaro Fukuda, Tommy W Terooatea, Aki Minoda, Akiharu Kubo, and Masayuki Amagai (https://doi.org/10.1016/j.jid.2023.08.008(opens in new tab/window)). It appears online in the Journal of Investigative Dermatology, volume 143, issue 12(December 2023), published by Elsevier.

The article is openly available at https://www.jidonline.org/article/S0022-202X(23)02560-5/fulltext(opens in new tab/window). An accompanying video is posted at https://www.youtube.com/shorts/D_YB1KVPElw(opens in new tab/window).

The full text of the article is also available to credentialed journalists upon request; contact Theresa Monturano at +1 215 239 3711 or[email protected](opens in new tab/window). Journalists wishing to interview the authors should contact Masayuki Amagai, MD, PhD, at [email protected](opens in new tab/window), or Umi Tahara at [email protected](opens in new tab/window).

This study was financially supported by the Japan Agency for Medical Research and Development (grant number: 21gm1010001) and by the Japan Society for the Promotion of Science Grant-in-Aid for Scientific Research (S) (grant number: JP22H04994).

The authors wish to thank Dr. Aki Minoda and Dr. Tommy W. Terooatea for their contributions during this research. Their analyses were very helpful in directly validating the presence of hemoglobin in keratinocytes, free from red blood cells.

About the Journal of Investigative Dermatology

The Journal of Investigative Dermatology(opens in new tab/window) (JID) is the official journal of the Society of Investigative Dermatology and the European Society for Dermatological Research. JID publishes high impact reports describing original research related to all aspects of cutaneous biology and skin diseases. Descriptions of important findings that result from basic, translational, or clinical research are published. Clinical research can include, but is not limited to, interventional trials, genetics studies, epidemiology, and health services research. www.jidonline.org(opens in new tab/window)

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