Casticin attenuates liver fibrosis and hepatic stellate cell activation by blocking TGF-β/Smad signaling pathway
| Autor: | Xiaoying Dong, Wanfu Xu, Yan Ding, Ling Zhou, Ting Li, Hang Zheng, Xiaojun Lin, Xiaochun Bai, Chunhong Jia, Mingqiang Lai, Linlin Wang, Lanlan Shan, Meng Dai |
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| Rok vydání: | 2017 |
| Předmět: |
CCl4
0301 basic medicine Pathology medicine.medical_specialty CCL4 SMAD 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine casticin In vivo Fibrosis Medicine TGF-β/Smad liver fibrosis hepatic stellate cell business.industry medicine.disease Hepatic stellate cell activation 030104 developmental biology Oncology chemistry Apoptosis 030220 oncology & carcinogenesis Cancer research Casticin Hepatic stellate cell business Research Paper |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| DOI: | 10.18632/oncotarget.17453 |
| Popis: | // Ling Zhou 1, * , Xiaoying Dong 1, * , Linlin Wang 1 , Lanlan Shan 2 , Ting Li 3 , Wanfu Xu 4 , Yan Ding 2 , Mingqiang Lai 5 , Xiaojun Lin 5 , Meng Dai 2 , Xiaochun Bai 5 , Chunhong Jia 5 and Hang Zheng 1 1 Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China 2 Department of Health Management, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China 3 Department of Hepatobiliary Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China 4 Department of Gastroenterology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, China 5 Department of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China * These authors contributed equally to this work Correspondence to: Chunhong Jia, email: nmjiachunhong@163.com Hang Zheng, email: zhengh001@163.com Keywords: casticin, CCl 4 , liver fibrosis, hepatic stellate cell, TGF-β/Smad Received: May 24, 2016 Accepted: April 14, 2017 Published: April 27, 2017 ABSTRACT Although many advances have been made in understanding the pathogenesis of liver fibrosis, few options are available for treatment. Casticin, one of the major flavonoids in Fructus Viticis extracts, has shown hepatoprotective potential, but its effects on liver fibrosis are not clear. In this study, we investigated the antifibrotic activity of casticin and its underlying mechanism in vivo and in vitro . Male mice were injected intraperitoneally with carbon tetrachloride (CCl 4 ) or underwent bile duct ligation (BDL) to induce liver fibrosis, followed by treatment with casticin or vehicle. In addition, transforming growth factor-β1(TGF-β1)-activated LX-2 cells were used. In vivo experiments showed that treatment with casticin alone had no toxic effect while significantly attenuating CCl 4 -or BDL-induced liver fibrosis, as indicated by reductions in the density of fibrosis, hydroxyproline content, expression of α-SMA and collagen α1(I) mRNA. Moreover, casticin inhibited LX2 proliferation, induced apoptosis in a time- and dose-dependent manner in vitro . The underlying molecular mechanisms for the effect of casticin involved inhibition of hepatic stellate cell (HSC) activation and reduced the expression of matrix metalloproteinase (MMP)-2, MMP-9, tissue inhibitor of metalloproteinases (TIMP)-1 and TIMP-2 resulting from blocking TGF-β1/Smad signaling, as well as increased the apoptosis of HSCs. The results suggest that casticin has potential benefits in the attenuation and treatment of liver fibrosis. |
| Databáze: | OpenAIRE |
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