期刊
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY
卷 64, 期 3, 页码 218-227出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/FJC.0000000000000109
关键词
scutellarin; human retinal endothelial cells; angiogenesis; diabetic retinopathy
资金
- National Natural Science Foundation of China [81100216]
- Science and technology projects of Liaoning Province [2012225079, 20102250002]
- Science and technology projects of Shenyang City [130084]
- scientific research of the First Hospital of China Medical University [FSFH1201]
Scutellarin inhibits hypoxia-induced and moderately high glucose-induced proliferation and vascular endothelial growth factor (VEGF) expression in human retinal endothelial cells (HRECs); thus, it could be a potential therapy for diabetic retinopathy. However, how scutellarin inhibits VEGF is unknown. In our study, HRECs were treated with high glucose and/or hypoxia-mimetic agent cobalt chloride to stimulate cell proliferation, migration, and angiogenesis, and the effects of scutellarin on these processes were analyzed through cell viability assay, Transwell migration assay and endothelial tube formation assay, respectively. The inhibition of angiogenic factor VEGF by scutellarin was confirmed by reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay. The mechanisms for VEGF inhibition were examined by luciferase reporter assay, Western blot, immunoprecipitation, and biochemical assays. We found that scutellarin not only concentration-dependently inhibited cell proliferation, migration, and tube formation in HRECs but also decreased their production of VEGF. The reduction of VEGF was due to increased ubiquitination and degradation of hypoxia-inducible factor (HIF)-1 alpha by scutellarin. Furthermore, scutellarin impaired the interaction of HIF-1 alpha with p300, which further decreased the transcriptional activity of HIF-1 alpha. As an inducer of HIF-1 alpha, oxidative stress was attenuated by scutellarin. Our data demonstrate that scutellarin exhibits an antiangiogenic effect via inhibition of oxidative stress, enhancement of HIF-1 alpha degradation, and reduction of VEGF secretion.
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