期刊
ONCOTARGET
卷 8, 期 49, 页码 86206-86216出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.21039
关键词
YC-1; hypoxia-inducible factor-1 alpha; angiogenesis; inflammation; fibrosis
资金
- Ministry of Science and Technology, Taipei, Taiwan [MOST 102-2320-B182-015-MY3, 103-2320-B182-002-MY3]
- Chang Gung Memorial Hospital, Taoyuan, Taiwan [CMRPD1A0621, CMRPD1D0351, CMRPD1D0352]
Hypoxia has been shown to have a role in the pathogenesis of several forms of liver disease. The aim of the study was to evaluate the mechanisms of HIF-1 alpha inhibitor, YC-1, during bile duct ligation (BDL)-induced liver fibrosis in mice. Liver fibrosis was induced in mice, and YC-1 was then given intraperitoneally (50 mg/kg) once daily following 5 days. Liver injuries mice that were treated with YC-1 showed improved inflammatory response and diminished angiogenesis and hepatic fibrosis. YC-1 treatment inhibited liver neutrophil infiltration, while a decreased in TNF-alpha signaling as well as macrophage aggregation. In addition, YC-1 downregulates iNOS and COX-2 levels by inhibiting the activation of NF-kappa B and STAT3 phosphorylation by negative regulation the expression of SOCS1 and SOCS3 signaling. On the other hand, YC-1 decreased angiogenesis, as shown by the downregulation of hypoxia-inducible cascade genes, i.e. VEGF. YC-1 treatment resulted in a significant decrease in hepatic fibrogenesis, alpha-SMA abundance, and TGF-beta R1 expression as well as hypoxia were assessed using VEGFR1, vWF and HIF-1 alpha immunostaining. These results suggest that multi-targeted therapies directed against angiogenesis, hypoxia, and fibrosis. Therefore, it may be suggested that YC-1 treatment may be a novel therapeutic agent for the treatment of liver disease.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据