LPCAT1 facilitates keratinocyte hyperproliferation and skin inflammation in psoriasis via regulating GLUT3

ABSTRACT Psoriasis is a chronic and relapsing inflammatory skin disorder characterized by keratinocyte hyperproliferation and immune cell infiltration. Lysophosphatidylcholine acyltransferase 1 (LPCAT1) has been identified as a cancer promoter in cutaneous squamous cell carcinoma by us, yet its role in psoriasis remains elusive. In this study, we report that LPCAT1 is highly expressed in psoriatic skin lesions. LPCAT1 promotes keratinocyte hyperproliferation and enhances the secretion of IL-1β, IL-6, CXCL10, CCL20, S100A9, and platelet-activating factor (PAF). In psoriasiform keratinocytes, LPCAT1 promotes proliferation and inflammatory mediator production by activating protein kinase B/NF-κB and STAT3 signaling pathways. Furthermore, LPCAT1 inhibition attenuated epidermal hyperplasia and relieved skin inflammation in imiquimod (IMQ)-treated mice. Importantly, we identify the glucose transporter GLUT3, a recently reported promising target to mitigate Th17-cell-mediated inflammatory diseases, as a critical downstream effector of LPCAT1. GLUT3 deficiency impaired the proliferation and inflammation of psoriatic keratinocytes. LPCAT1 regulates GLUT3 in keratinocytes via NF-κB/STAT3 signaling, enhancing keratinocyte glycolysis and promoting pro-proliferative and proinflammatory effects. In addition, suppressing GLUT3 in mice alleviated IMQ-induced dermatitis. Taken together, our study indicates the critical role of the LPCAT1-GLUT3 axis in psoriasis pathogenesis and proposes LPCAT1 or GLUT3 as a potential therapeutic target for psoriasis.

文章引用产品列表