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.

中文翻译：

---

皮肤稳态和损伤中不同的葡萄糖需求确定了牛皮癣的治疗目标。

与静止细胞相比，增殖细胞更依赖于葡萄糖的生长。尽管角质形成细胞中的葡萄糖转运主要是由Glut1促进转运蛋白介导的，但我们发现Glut1的角质形成细胞特异性消融不会损害小鼠皮肤的发育和体内稳态。体外代谢谱分析显示，在Glut1缺陷型角质形成细胞中，鞘脂，己糖，氨基酸和核苷酸代谢发生改变，从而提示代谢适应。但是，培养的缺乏Glut1的角质形成细胞表现出代谢和氧化应激，并损害了增殖。同样，Glut1缺乏会损害体内角质形成细胞的增殖和在受伤或受紫外线损伤的小鼠皮肤内的迁移。尤其，遗传和药理学上的Glut1失活均能减少牛皮癣样疾病小鼠模型中的增生。在这些模型中局部应用Glut1抑制剂也可以减少炎症。Glut1抑制降低了人类银屑病皮肤类器官中与病理相关的基因的表达。因此，Glut1被选择性地用于损伤和炎症相关的角质形成细胞的增殖，其抑制作用为牛皮癣提供了一种新颖的治疗策略。