Astragaloside IV improves angiogenesis under hypoxic conditions by enhancing hypoxia‑inducible factor‑1α SUMOylation
| Autor: | Chunyan Zhang, Tian Yu, Baoshen Wang, Changqing Hu, Xiaozhi Liu, Dongmei Chu, Xiaofang Ma |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Cancer Research
Angiogenesis SUMO protein Neovascularization Physiologic Biochemistry angiogenesis chemistry.chemical_compound Human Umbilical Vein Endothelial Cells Genetics medicine Humans hypoxia inducible factor-1α Molecular Biology hypoxia Chemistry astragaloside IV small ubiquitin-related modifier 1 Sumoylation Articles Saponins Cell cycle Hypoxia (medical) Hypoxia-Inducible Factor 1 alpha Subunit Cell Hypoxia Triterpenes Cell biology Vascular endothelial growth factor medicine.anatomical_structure Oncology Hypoxia-inducible factors Small ubiquitin-related modifier 1 Molecular Medicine medicine.symptom Blood vessel |
| Zdroj: | Molecular Medicine Reports |
| ISSN: | 1791-3004 1791-2997 |
| DOI: | 10.3892/mmr.2021.11883 |
| Popis: | Improving angiogenic capacity under hypoxic conditions is essential for improving the survival of skin grafts, as they often lack the necessary blood supply. The stable expression levels of hypoxia-inducible factor-1α (HIF-1α) in the nucleus directly affect the downstream vascular endothelial growth factor (VEGF) signaling pathway and regulate angiogenesis in a hypoxic environment. Astragaloside IV (AS-IV), an active component isolated from Astragalus membranaceus, has multiple biological effects including antioxidant and anti-diabetic effects, and the ability to provide protection from cardiovascular damage. However, the mechanisms underlying these effects have not previously been elucidated. The present study investigated whether AS-IV promotes angiogenesis via affecting the balance between ubiquitination and small ubiquitin-related modifier (SUMO) modification of HIF-1α. The results demonstrated that persistent hypoxia induces changes in expression levels of HIF-1α protein and significantly increases the proportion of dysplastic blood vessels. Further western blotting experiments showed that rapid attenuation and delayed compensation of SUMO1 activity is one of the reasons for the initial increase then decrease in HIF-1α levels. SUMO1 overexpression stabilized the presence of HIF-1α in the nucleus and decreased the extent of abnormal blood vessel morphology observed following hypoxia. AS-IV induces vascular endothelial cells to continuously produce SUMO1, stabilizes the HIF-1α/VEGF pathway and improves angiogenesis in hypoxic conditions. In summary, the present study confirmed that AS-IV stimulates vascular endothelial cells to continuously resupply SUMO1, stabilizes the presence of HIF-1α protein and improves angiogenesis in adverse hypoxic conditions, which may improve the success rate of flap graft surgery following trauma or burn. |
| Databáze: | OpenAIRE |
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