Title |
Asiatic Acid Inhibits Liver Fibrosis by Blocking TGF-beta/Smad Signaling In Vivo and In Vitro
|
---|---|
Published in |
PLOS ONE, February 2012
|
DOI | 10.1371/journal.pone.0031350 |
Pubmed ID | |
Authors |
Li-xia Tang, Rui-hua He, Guang Yang, Jia-ju Tan, Li Zhou, Xiao-ming Meng, Xiao Ru Huang, Hui Yao Lan |
Abstract |
Liver fibrosis is a major cause of liver failure, but treatment remains ineffective. In the present study, we investigated the mechanisms and anti-hepatofibrotic activities of asiatic acid (AA) in a rat model of liver fibrosis induced by carbon tetrachloride (CCl(4)) and in vitro in TGF-beta1-stimulated rat hepatic stellate cell line (HSC-T6). Treatment with AA significantly attenuated CCl(4)-induced liver fibrosis and functional impairment in a dosage-dependent manner, including blockade of the activation of HSC as determined by inhibiting de novo alpha smooth muscle actin (a-SMA) and collagen matrix expression, and an increase in ALT and AST (all p<0.01). The hepatoprotective effects of AA on fibrosis were associated with upregulation of hepatic Smad7, an inhibitor of TGF-beta signaling, thereby blocking upregulation of TGF-beta1 and CTGF and the activation of TGF-beta/Smad signaling. The anti-fibrosis activity and mechanisms of AA were further detected in vitro in HSC-T6. Addition of AA significantly induced Smad7 expression by HSC-T6 cells, thereby inhibiting TGF-beta1-induced Smad2/3 activation, myofibroblast transformation, and collagen matrix expression in a dosage-dependent manner. In contrast, knockdown of Smad7 in HSC-T6 cells prevented AA-induced inhibition of HSC-T6 cell activation and fibrosis in response to TGF-beta1, revealing an essential role for Smad7 in AA-induced anti-fibrotic activities during liver fibrosis in vivo and in vitro. In conclusion, AA may be a novel therapeutic agent for liver fibrosis. Induction of Smad7-dependent inhibition of TGF-beta/Smad-mediated fibrogenesis may be a central mechanism by which AA protects liver from injury. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United Kingdom | 1 | 1% |
Unknown | 81 | 99% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 14 | 17% |
Researcher | 10 | 12% |
Student > Bachelor | 10 | 12% |
Student > Master | 10 | 12% |
Other | 8 | 10% |
Other | 13 | 16% |
Unknown | 17 | 21% |
Readers by discipline | Count | As % |
---|---|---|
Medicine and Dentistry | 21 | 26% |
Agricultural and Biological Sciences | 15 | 18% |
Biochemistry, Genetics and Molecular Biology | 8 | 10% |
Pharmacology, Toxicology and Pharmaceutical Science | 3 | 4% |
Social Sciences | 3 | 4% |
Other | 11 | 13% |
Unknown | 21 | 26% |