Interplay of HIF-1α, SMAD2, and VEGF signaling in hypoxic renal environments: impact on macrophage polarization and renoprotection.

ABSTRACT: This study investigates the roles of hypoxia-inducible factor (HIF-1α), SMAD2, and vascular endothelial growth factor (VEGF) in renal repair under hypoxic conditions, focusing on their impact on macrophage phenotype transformation. Bioinformatics analysis identified SMAD2 as a key gene in renal injury, correlating with HIF-1α and VEGF levels. In a cohort of 60 pediatric patients, non-AKI individuals exhibited higher VEGF and SMAD2 levels but lower HIF-1α compared to AKI patients. Using a chronic hypoxia rat model, bevacizumab treatment exacerbated renal damage, as indicated by elevated serum creatinine (79.4 ± 61.7 μmol/L), increased inflammatory markers, and heightened HIF-1α expression. Bevacizumab's inhibition of VEGF also impaired macrophage phenotype modulation. In vitro experi

SUBMITTER: Xu Y 

PROVIDER: S-EPMC12462414 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature