HMGB1 mediates low-dose ionizing radiation-induced Wnt/β-catenin activation in SRA01/04 cells: Mechanistic clues to early cataractogenesis.

Emerging evidence from our prior investigations has elucidated the dose-dependent regulatory effects of low-dose ionizing radiation on cellular behaviors including proliferation, migration and differentiation in HLE-B3 lens epithelial cells, with concomitant activation of the canonical Wnt/β-catenin signaling cascade. To extend these findings to alternative cellular models, the present study systematically evaluated the biological responses of the well-characterized human lens epithelial cell line SRA01/04 to low-dose ionizing radiation exposure (0.05-0.2 Gy) versus high-dose radiation (0.5-2 Gy), with particular emphasis on temporal dynamics during acute (0-72 h) and chronic (7 days) phases. Mechanistically, lentivirus-mediated RNA interference was employed to establish stable High mobility group box protein 1 (HMGB1)-knockdown cell models, enabling rigorous interrogation of β-catenin subcellular localization and functional readouts under 0, 0.1 and 0.2 Gy γ-ray exposures. Key findings revealed the following: i) low-dose ionizing radiation within the 0.05-0.2 Gy range significantly potentiated SRA01/04 cell proliferation and migration capacity (P<0.05), concomitant with nuclear accumulation of β-catenin; ii) genetic ablation of HMGB1 abolished radiation-induced β-catenin nuclear translocation, resulting in 77% reduction in proliferation rate and 82% suppression of migratory activity compared with wild-type counterparts under equivalent radiation. The experimental evidence identifies HMGB1-mediated signaling as the critical molecular nexus connecting low-dose ionizing radiation exposure to dysregulated Wnt/β-catenin activity in lens epithelium, offering a new therapeutic target for preventing radiation-related cataracts.