Sweet skin remedy

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Science Translational Medicine  09 May 2018:
Vol. 10, Issue 440, eaat8526
DOI: 10.1126/scitranslmed.aat8526


Up-regulation of glucose transport drives keratinocyte proliferation, whereas its inhibition offers therapeutic potential against psoriasis.

Glucose is the preferred energy substrate of many proliferative cell types. It is not only used to provide ATP as energy currency, but it also supplies the building blocks that allow cell growth. Keratinocytes are among the cells that take up large amounts of glucose to maintain skin homeostasis. Still, the mechanisms underlying metabolic regulation in keratinocytes and their role in determining skin health are not well understood.

Zhang and colleagues identified the glucose transporter GLUT1 as an important regulator of glucose uptake in keratinocytes. Specifically deleting Glut1 from keratinocytes led to markedly reduced proliferation in vitro, but the skin of Glut1-deficient mice developed normally, possibly because of adaptive changes in lipid metabolism. Strikingly, Glut1-deficient keratinocytes had higher levels of oxidative stress markers, and growing the cells under stress conditions such as H2O2 exposure confirmed that these cells are more prone to die under these circumstances. The importance of this stress response was even more evident in vivo. Glut1 knockout mice that were subjected to physiological insults like UV-B irradiation or scratch wounding recovered more slowly.

With this in mind, the authors took an interesting approach and applied their experimental setup to models of psoriasis. Psoriasis is an inflammatory skin disease that is characterized by keratinocyte hyperproliferation and can be mimicked in mice using topical application of imiquimod or injection of IL-23. Deletion of Glut1 from keratinocytes prevented skin hyperplasia normally induced by these two methods. What’s more, topical inhibition of glucose transport led to a similar attenuation of skin inflammation and thickening.

Altogether, the work described here is a promising new step toward medication against psoriasis. GLUT1 expression is also increased in psoriatic plaques of patients, and clinical tests to show the therapeutic potential of topically applied glucose transport inhibitors will be eagerly awaited.

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