Exp Cell Res. 2026 Feb 2:114922. doi: 10.1016/j.yexcr.2026.114922. Online ahead of print.
ABSTRACT
Proliferative diabetic retinopathy (PDR) is characterized by pathological angiogenesis and endothelial dysfunction driven by hyperglycemia. Ribosome biogenesis plays a crucial role in endothelial proliferation, yet its involvement in PDR remains unexplored. This study investigates the role of NOP14, a key regulator of ribosome biogenesis, in PDR progression and its interplay with Wnt/β-catenin signaling. NOP14 expression was elevated in PDR models and HG-treated human retinal endothelial cells (HRECs). Knockdown of NOP14 ameliorated retinal damage in PDR mice, decreased angiogenesis-related proteins (CD31, VEGFA, PDGF, ANG2). In vitro, NOP14 knockdown suppressed HG-induced endothelial proliferation, DNA synthesis, mitochondrial activity, and tube formation, accompanied by reduced ribosome biogenesis and promoted cell apoptosis. While overexpression of NOP14 exhibited the opposite effect to NOP14 knockdown on HG-induced HRECs. Mechanistically, NOP14 activated Wnt/β-catenin signaling, as evidenced by increased p-GSK-3β, β-catenin and Cyclin D1 levels and Wnt/β-catenin activity. Activation of Wnt/β-catenin signaling partially rescued the effects of NOP14 knockdown on endothelial dysfunction and ribosome biogenesis. NOP14 promotes PDR progression by driving ribosome biogenesis and endothelial dysfunction through Wnt/β-catenin signaling activation. Targeting the NOP14/Wnt/β-catenin axis offers a promising therapeutic strategy for mitigating pathological angiogenesis in PDR.
PMID:41638389 | DOI:10.1016/j.yexcr.2026.114922