GSK3β Negatively Regulates LPS-induced Osteopontin Expression via Inhibiting its Transcription

Abstract

Osteopontin (OPN) is expressed by a variety of immune cells and is critical for both innate and adaptive immune responses. The expression status of OPN might be tightly regulated to maintain immune homeostasis. However, the mechanisms by which OPN is negatively regulated in LPS-stimulated macrophages remain largely unknown. In this study, we showed that glycogen synthase kinase 3β (GSK3β) inhibitors - SB216763, LiCl and azakenpaullone - enhanced LPS-induced OPN expression in mouse peritoneal macrophages. GSK3β knock-down had the similar effects. Furthermore, we found that GSK3β inhibitors and GSK3β knock-down both increased the activity of OPN promoter in LPS-stimulated macrophages. GSK3β inhibitor-mediated enhancement of LPS-induced OPN promoter activity was abrogated in GSK3β siRNA-treated macrophages. Therefore, we identified GSK3β as a negative regulator of OPN expression and suggest GSK3β as a potential therapeutic target for the intervention of diseases with uncontrolled OPN production.