Differential glucose requirement in skin homeostasis and injury identifies a therapeutic target for psoriasis.

Journal Article (Journal Article)

Proliferating cells, compared with quiescent cells, are more dependent on glucose for their growth. Although glucose transport in keratinocytes is mediated largely by the Glut1 facilitative transporter, we found that keratinocyte-specific ablation of Glut1 did not compromise mouse skin development and homeostasis. Ex vivo metabolic profiling revealed altered sphingolipid, hexose, amino acid, and nucleotide metabolism in Glut1-deficient keratinocytes, thus suggesting metabolic adaptation. However, cultured Glut1-deficient keratinocytes displayed metabolic and oxidative stress and impaired proliferation. Similarly, Glut1 deficiency impaired in vivo keratinocyte proliferation and migration within wounded or UV-damaged mouse skin. Notably, both genetic and pharmacological Glut1 inactivation decreased hyperplasia in mouse models of psoriasis-like disease. Topical application of a Glut1 inhibitor also decreased inflammation in these models. Glut1 inhibition decreased the expression of pathology-associated genes in human psoriatic skin organoids. Thus, Glut1 is selectively required for injury- and inflammation-associated keratinocyte proliferation, and its inhibition offers a novel treatment strategy for psoriasis.

Full Text

Duke Authors

Cited Authors

  • Zhang, Z; Zi, Z; Lee, EE; Zhao, J; Contreras, DC; South, AP; Abel, ED; Chong, BF; Vandergriff, T; Hosler, GA; Scherer, PE; Mettlen, M; Rathmell, JC; DeBerardinis, RJ; Wang, RC

Published Date

  • May 2018

Published In

Volume / Issue

  • 24 / 5

Start / End Page

  • 617 - 627

PubMed ID

  • 29662201

Pubmed Central ID

  • PMC6095711

Electronic International Standard Serial Number (EISSN)

  • 1546-170X

Digital Object Identifier (DOI)

  • 10.1038/s41591-018-0003-0


  • eng

Conference Location

  • United States