GBP2 inhibits pathological angiogenesis in the retina via the AKT/mTOR/VEGFA axis.

Pathological retinal angiogenesis is not only the hallmark of retinopathies, but also a major cause of blindness. Guanylate binding protein 2 (GBP2) has been reported to be associated with retinal diseases such as diabetic retinopathy and hypoxic retinopathy. However, GBP2-mediated pathological retinal angiogenesis remains largely unknown. The present study aimed to investigate the role of GBP2 in pathological retinal angiogenesis and its underlying molecular mechanism. In this study, we established oxygen-induced retinopathy (OIR) mice model for in vivo study and hypoxia-induced angiogenesis in ARPE-19 cells for in vitro study. We demonstrated that GBP2 expression was markedly downregulated in the retina of mice with OIR and ARPE-19 cells treated with hypoxia, which was associated with pathological retinal angiogenesis. The regulatory mechanism of GBP2 in ARPE-19 cells was studied by GBP2 silencing and overexpression. The regulatory mechanism of GBP2 in the retina was investigated by overexpressing GBP2 in the retina of OIR mice. Mechanistically, GBP2 downregulated the expression and secretion of vascular endothelial growth factor (VEGFA) in ARPE-19 cells and retina of OIR mice. Interestingly, overexpression of GBP2 significantly inhibited neovascularization in OIR mice, conditioned medium of GBP2 overexpressing ARPE-19 cells inhibited angiogenesis in human umbilical vein endothelial cells (HUVECs). Furthermore, we confirmed that GBP2 downregulated VEGFA expression and angiogenesis by inhibiting the AKT/mTOR signaling pathway. Taken together, we concluded that GBP2 inhibited pathological retinal angiogenesis via the AKT/mTOR/VEGFA axis, thereby suggesting that GBP2 may be a therapeutic target for pathological retinal angiogenesis.

GBP2 promotes clear cell renal cell carcinoma progression through immune infiltration and regulation of PD­L1 expression via STAT1 signaling.

Guanylate­binding protein 2 (GBP2) has been widely studied in cancer, however, its potential role in clear cell renal cell carcinoma (ccRCC) is not fully elucidated. The present study aimed to explore the effect of GBP2 on tumor progression and its possible underlying molecular mechanisms in ccRCC. The Cancer Genome Atlas, Gene Expression Omnibus, Cancer Cell Line Encyclopedia databases, and several bioinformatics analysis tools, such as Gene Expression Profiling Interactive Analysis 2, Kaplan­Meier plotter, UALCAN, LinkedOmics, Metascape, GeneMANIA and Tumor Immune Estimation Resource, were used to characterize the functional relationship between GBP2 and ccRCC. Focusing on the association between GBP2 and programmed death ligand 1 (PD­L1) in vitro, the regulatory mechanism was investigated by knockdown and overexpression of GBP2 in Caki­1 and 786­O cells using reverse transcription­quantitative PCR, western blotting and co­immunoprecipitation techniques. The results indicated that GBP2 was commonly upregulated in ccRCC, correlating with worse prognosis. In addition, GBP2 expression levels were positively associated with different patterns of immune cell infiltration, suggesting that the GBP2 gene regulates PD­L1 expression via the signal transducer and activator of transcription 1 (STAT1) pathway. The present study suggested that GBP2 regulates tumor immune infiltration and promotes tumor immune escape through PD­L1 expression, revealing a potential immunotherapeutic target for ccRCC.