Identification of specifically activated angiogenic molecules in HMGB-1-induced angiogenesis

Abstract

High-mobility group box-1 (HMGB-1) is expressed in almost all cells, and its dysregulated expression correlates with inflammatory diseases, ischemia, and cancer. Some of these conditions accompany HMGB-1-mediated abnormal angiogenesis. Thus far, the mechanism of HMGB-1-induced angiogenesis remains largely unknown. In this study, we performed time-dependent DNA microarray analysis of endothelial cells (ECs) after HMGB-1 or VEGF treatment. The pathway analysis of each gene set upregulated by HMGB-1 or VEGF showed that most HMGB-1-induced angiogenic pathways were also activated by VEGF, although the activation time and gene sets belonging to the pathways differed. In addition, HMGB-1 upregulated some VEGFR signaling-related angiogenic factors including EGR1 and, importantly, novel angiogenic factors, such as ABL2, CEACAM1, KIT, and VIPR1, which are reported to independently promote angiogenesis under physiological and pathological conditions. Our findings suggest that HMGB-1 independently induces angiogenesis by activating HMGB-1-specific angiogenic factors and also functions as an accelerator for VEGF-mediated conventional angiogenesis.

High‐mobility group box 1 protein modulated proliferation and radioresistance in esophageal squamous cell carcinoma

“…In the cytoplasm, HMGB1 can control programmed cell death . As a damage‐associated molecular pattern molecule, the role of HMGB1 is more complex; it involves apoptosis, epithelial‐mesenchymal transition, angiogenesis, and immune regulation . Based on the aforementioned evidence, we explored some factors related to radioresistance in ESCC cell lines.…”

“…In the cytoplasm, HMGB1 is a core protein that contributes to autophagy and apoptosis imbalance . As a damage‐associated molecular pattern molecule, HMGB1 can be actively or passively released into the extracellular fluid after stress and regulate the metastasis, angiogenesis, and immunogenicity of tumor cells …”