Withagulatin A inhibits hepatic stellate cell viability and procollagen I production through Akt and Smad signaling pathways
文献类型：期刊论文
| 作者 | Liu, Qiong; Chen, Jing ; Wang, Xu; Yu, Liang; Hu, Li-hong; Shen, Xu
|
| 刊名 | ACTA PHARMACOLOGICA SINICA
 |
| 出版日期 | 2010-08 |
| 卷号 | 31期号:8页码:944-952 |
| 关键词 | liver fibrosis collagen hepatic stellate cell Akt Smad |
| ISSN号 | 1671-4083 |
| DOI | 10.1038/aps.2010.72 |
| 文献子类 | Article |
| 英文摘要 | Aim: To investigate the effects of the natural product Withagulatin A on hepatic stellate cell (HSC) viability and type I procollagen production. The potential mechanism underlying the pharmacological actions was also explored. Methods: The effect of Withagulatin A on cell viability was evaluated in HSC and LX-2 cells using a sulforhodamine B (SRB) assay. Cell cycle distribution was analyzed using flow cytometry. Type I procollagen gene expression was determined using real-time PCR. Regulation of signaling molecules by Withagulatin A was detected using western blotting. Results: Primary rat HSCs and the human hepatic stellate cell line LX-2 treated with Withagulatin A (0.625-20 mu mol/L) underwent a dose-dependent decrease in cell viability, which was associated with S phase arrest and the induction of cell apoptosis. In addition, the natural product decreased phosphorylation of the Akt/mTOR/p70S6K pathway that controls cell proliferation and survival. Furthermore, Withagulatin A (1, 2 mu mol/L) inhibited transforming growth factor-beta (TGF-beta) stimulated type I procollagen gene expression, which was attributable to the suppression of TGF-beta stimulated Smad2 and Smad3 phosphorylation. Conclusion: Our results demonstrated that Withagulatin A potently inhibited HSC viability and type I procollagen production, thereby implying that this natural product has potential use in the development of anti-fibrogenic reagents for the treatment of hepatic fibrosis. |
| WOS关键词 | PHYSALIS-ANGULATA L ; FIBROSIS ; PROLIFERATION ; MECHANISMS ; EXPRESSION ; LIVER ; PHOSPHORYLATION ; WITHANOLIDES ; FIBROGENESIS ; LIPOCYTES |
| 资助项目 | National Natural Science Foundation of China[20721003] ; National Natural Science Foundation of China[90713046] ; State Key Program of Basic Research of China[2009CB918502] ; State Key Program of Basic Research of China[2010CB912501] ; Shanghai Basic Research Project[09QA1406800] ; Foundation of Chinese Academy of Sciences[KSCX1-YW-02-2] ; Key New Drug Creation and Manufacturing Program[2009ZX09301-001] |
| WOS研究方向 | Chemistry ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| CSCD记录号 | CSCD:3971253 |
| WOS记录号 | WOS:000280617100008 |
| 出版者 | SHANGHAI INST MATERIA MEDICA |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/278804]  |
| 专题 | 上海中药现代化研究中心 中科院受体结构与功能重点实验室 新药研究国家重点实验室 药理学第三研究室 |
| 通讯作者 | Hu, Li-hong |
| 作者单位 | Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Liu, Qiong,Chen, Jing,Wang, Xu,et al. Withagulatin A inhibits hepatic stellate cell viability and procollagen I production through Akt and Smad signaling pathways[J]. ACTA PHARMACOLOGICA SINICA,2010,31(8):944-952. |
| APA | Liu, Qiong,Chen, Jing,Wang, Xu,Yu, Liang,Hu, Li-hong,&Shen, Xu.(2010).Withagulatin A inhibits hepatic stellate cell viability and procollagen I production through Akt and Smad signaling pathways.ACTA PHARMACOLOGICA SINICA,31(8),944-952. |
| MLA | Liu, Qiong,et al."Withagulatin A inhibits hepatic stellate cell viability and procollagen I production through Akt and Smad signaling pathways".ACTA PHARMACOLOGICA SINICA 31.8(2010):944-952. |
入库方式： OAI收割
来源：上海药物研究所
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。