Regulation of lipoprotein processing by GPNMB in foamy macrophages: potential therapeutic targets for atherosclerosis.

ABSTRACT: The formation of foamy macrophages is often considered a pathological hallmark of atherosclerosis, but the underlying mechanisms remain elusive. Herein, we demonstrated that the transcription factor TFEC could upregulate the expression of Glycoprotein non-metastatic melanoma protein B (GPNMB) in atherosclerotic plaque foamy macrophages. Circulating levels of soluble GPNMB correlated positively with atherosclerotic severity. Moreover, mice with systemic Gpnmb-mutation or myeloid-specific Gpnmb knockout exhibited a reduced atherosclerotic burden. Live-cell imaging revealed that GPNMB-positive vesicles were involved in lipoprotein internalization and transport within macrophages and facilitated lipid droplet formation. In Gpnmb-mutant macrophages, impaired lipid droplet formation from interna

SUBMITTER: Wang J 

PROVIDER: S-EPMC12618667 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature