期刊
JOURNAL OF CELLULAR BIOCHEMISTRY
卷 119, 期 2, 页码 2258-2268出版社
WILEY
DOI: 10.1002/jcb.26388
关键词
angiogenesis; HIF-1; liver fibrosis; oroxylin A; YAP
资金
- National Natural Science Foundation of China [81270514, 31401210, 31571455, 31600653, 81600483]
- Program for Graduate Scientific Innovation [KYLX15_0999]
- Youth Natural Science Foundation of Jiangsu Province [BK20140955]
- Open Project Program of Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica [JKLPSE 201502]
- Project of the Priority Academic Program Development of Jiangsu Higher Education Institutions [(PAPD)]
Angiogenesis of liver sinusoidal endothelial cells (LSECs) accompanies with hypoxia in liver fibrosis and they are of mutual promotion, which has raised wide concern. Here we established murine model of liver fibrosis and found that oroxylin A (40mg/kg) could ameliorate angiogenesis in liver fibrosis may related to hypoxia inducible factor 1 (HIF-1). The underlying mechanism was further investigated by isolating and culturing murine primary LSECs. Hypoxia induced vascular endothelial growth factor A (VEGF-A), angiopoietin 2 (Ang-2), and platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31) elevated in LSECs were reduced by oroxylin A or acriflavine (ACF, an HIF-1 inhibitor), indicating HIF-1 involved the angiogenesis of LSECs. Additionally, interference with Yes-associated protein (YAP) significant downregulated the protein expression of HIF-1 and VEGF-A, while YAP plasmid exhibited an opposite effect. We next found that oroxylin A inhibited hypoxia-induced nuclear translocation of YAP, which may influence the accumulation of HIF-1 and subsequently decrease transcription of downstream target gene including VEGF-A and Ang-2, thereby exerting an anti-angiogenic activity.
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