Effects of 18α-glycyrrhizin on TGF-β1/Smad signaling pathway in rats with carbon tetrachloride-induced liver fibrosis

被引:0
作者
Qu, Ying [1 ]
Zong, Lei [1 ]
Xu, Mingyi [1 ]
Dong, Yuwei [1 ]
Lu, Lungen [1 ]
机构
[1] Shanghai Jiaotong Univ Sch Med, Shanghai Peoples Hosp 1, Dept Gastroenterol, Shanghai 200080, Peoples R China
来源
INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY | 2015年 / 8卷 / 02期
基金
中国国家自然科学基金;
关键词
18; alpha-glycyrrhizin; liver fibrosis; collagen; TGF-beta; 1; Smad; HEPATIC STELLATE CELLS; GROWTH-FACTOR-BETA; TGF-BETA; TRANSCRIPTIONAL REGULATION; EXPRESSION; SP1; ACTIVATION; COLLAGEN; SMAD; GLYCYRRHIZIN;
D O I
暂无
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: Glycyrrhizin has various pharmacological effects including hepato-protection. This study aimed to investigate the potential mechanism underlying the protective effects of 18 alpha-glycyrrhizin (18 alpha-GL) in rats with carbon tetrachloride (CCl4) induced liver fibrosis. Methods: Male Sprague-Dawley (SD) rats were randomly divided into control group, fibrosis group, 25 mg/kg 18 alpha-GL group and 12.5 mg/kg 18 alpha-GL group. Rats in experimental groups were subcutaneously injected with 40% CCl4 twice weekly for 8 weeks. Immunohistochemical examination was carried out to detect the protein expressions of collagen I, collagen III, TGF-beta 1, p-Smad2, p-Smad3, Smad 7 and SP-1, in the liver, and the mRNA and protein expressions of these genes were determined in the liver by real time PCR and Western blot assay, respectively. Results: 18 alpha-GL ameliorated histological changes and significantly suppressed collagen deposition. 18 alpha-GL significantly decreased the mRNA expressions of TGF-beta 1, Smad2, Smad3 and SP-1 in the liver. Immunohistochemical staining revealed that TGF-beta 1, p-Smad2, p-Smad3 and SP-1 expressions reduced following 18 alpha-GL therapy. Western blot assay showed p-Smad2, p-Smad3, smad2 and smad3 expressions decreased after 18 alpha-GL treatment. The mRNA and protein expression of Smad7 remained unchanged. Conclusion: 18 alpha-GL is able to attenuate CCl4 induced liver fibrosis in rat.
引用
收藏
页码:1292 / 1301
页数:10
相关论文
共 45 条
[1]   Anti-hepatitis C virus compounds obtained from Glycyrrhiza uralensis and other Glycyrrhiza species [J].
Adianti, Myrna ;
Aoki, Chie ;
Komoto, Mari ;
Deng, Lin ;
Shoji, Ikuo ;
Wahyuni, Tutik Sri ;
Lusida, Maria Inge ;
Soetjipto ;
Fuchino, Hiroyuki ;
Kawahara, Nobuo ;
Hotta, Hak .
MICROBIOLOGY AND IMMUNOLOGY, 2014, 58 (03) :180-187
[2]  
Ashfaq UA, 2011, J TRANSL MED, V9
[3]  
Briones-Orta Marco A, 2011, Curr Mol Pharmacol, V4, P141
[4]   Hepatic stellate cell/myofibroblast subpopulations in fibrotic human and rat livers [J].
Cassiman, D ;
Libbrecht, L ;
Desmet, V ;
Denef, C ;
Roskams, T .
JOURNAL OF HEPATOLOGY, 2002, 36 (02) :200-209
[5]   TRANSFORMING GROWTH FACTOR-BETA-1 AND FACTOR-ALPHA IN CHRONIC LIVER-DISEASE - EFFECTS OF INTERFERON ALFA THERAPY [J].
CASTILLA, A ;
PRIETO, J ;
FAUSTO, N .
NEW ENGLAND JOURNAL OF MEDICINE, 1991, 324 (14) :933-940
[6]   Smad7 prevents activation of hepatic stellate cells and liver fibrosis in rats [J].
Dooley, S ;
Hamzavi, J ;
Breitkopf, K ;
Wiercinska, E ;
Said, HM ;
Lorenzen, J ;
Ten Dijke, P ;
Gressner, AM .
GASTROENTEROLOGY, 2003, 125 (01) :178-191
[7]   Hepatocyte-specific Smad7 expression attenuates TGF-β-mediated fibrogenesis and protects against liver damage [J].
Dooley, Steven ;
Hamzavi, Jafar ;
Ciuclan, Loredana ;
Godoy, Patricio ;
Ilkavets, Iryna ;
Ehnert, Sabrina ;
Ueberham, Elke ;
Gebhardt, Rolf ;
Kanzler, Stephan ;
Geier, Andreas ;
Breitkopf, Katja ;
Weng, Honglei ;
Mertens, Peter R. .
GASTROENTEROLOGY, 2008, 135 (02) :642-659
[8]   TGF-β in progression of liver disease [J].
Dooley, Steven ;
ten Dijke, Peter .
CELL AND TISSUE RESEARCH, 2012, 347 (01) :245-256
[9]   The role and regulation of hepatic stellate cell apoptosis in reversal of liver fibrosis [J].
Elsharkawy, AM ;
Oakley, F ;
Mann, DA .
APOPTOSIS, 2005, 10 (05) :927-939
[10]  
Ferrucci Leah M, 2010, J Clin Gastroenterol, V44, pe40, DOI 10.1097/MCG.0b013e3181b766ed