scholarly journals Hepatocyte Growth Factor Attenuates Liver Fibrosis Induced by Bile Duct Ligation

2006 ◽  
Vol 168 (5) ◽  
pp. 1500-1512 ◽  
Author(s):  
Jing-Lin Xia ◽  
Chunsun Dai ◽  
George K. Michalopoulos ◽  
Youhua Liu
Keyword(s):  
Growth Factor ◽  
Bile Duct ◽  
Liver Fibrosis ◽  
Hepatocyte Growth Factor ◽  
Bile Duct Ligation ◽  
Duct Ligation ◽  
Hepatocyte Growth

Vitamin D inhibits development of liver fibrosis in an animal model but cannot ameliorate established cirrhosis

2015 ◽  
Vol 308 (2) ◽  
pp. G112-G120 ◽  
Author(s):  
Shirley Abramovitch ◽  
Efrat Sharvit ◽  
Yosef Weisman ◽  
Amir Bentov ◽  
Eli Brazowski ◽  
...  
Keyword(s):  
Vitamin D ◽  
Growth Factor ◽  
Bile Duct ◽  
Liver Fibrosis ◽  
Bile Duct Ligation ◽  
Active Form ◽  
Preventive Treatment ◽  
Antifibrotic Effect ◽  
Duct Ligation

1,25(OH)2D3, the active form of vitamin D, has an antiproliferative and antifibrotic effect on hepatic stellate cells. Our aim was to investigate the potential of 1,25(OH)2D3 to inhibit the development of liver fibrosis and to ameliorate established fibrosis in vivo. The antifibrotic effect of 1,25(OH)2D3 was investigated in a thioacetamide (TAA) model (as a preventive treatment and as a remedial treatment) and in a bile duct ligation model. In the preventive model, rats received simultaneously intraperitoneum injection of TAA and/or 1,25(OH)2D3 for 10 wk. In the remedial model, rats were treated with TAA for 10 wk and then received 1,25(OH)2D3 or saline for 8 wk. Fibrotic score was determined by Masson staining. Collagen I, α-smooth muscle actin (α-SMA), tissue inhibitor of metalloproteinase-1 (TIMP1), platelet-derived growth factor (PDGF), and transforming growth factor-β (TGF-β) expression were measured by Western blot analysis and real-time PCR. Hypercalemia was detected by chemistry measurements. Preventive treatment of 1,25(OH)2D3 significantly suppressed liver fibrosis both macroscopically and microscopically and significantly lowered the fibrotic score of the TAA + 1,25(OH)2D3 group compared with the TAA group. 1,25(OH)2D3 significantly inhibited expression of PDGF and TGF-β by ∼50% and suppressed the expression of collagen Iα1, TIMP1, and α-SMA by approximately three-, two-, and threefold, respectively. In contrast, 1,25(OH)2D3 was inefficient in amelioration of established liver fibrosis. Administration of 1,25(OH)2D3 to bile duct ligation rats led to a high mortality rate probably caused by hypercalcemia. We conclude that 1,25(OH)2D3 may be considered as a potential preventive treatment in an in vivo model but failed to ameliorate established cirrhosis.

scholarly journals Positive Effects of Ger-Gen-Chyn-Lian-Tang on Cholestatic Liver Fibrosis in Bile Duct Ligation-Challenged Mice

2019 ◽  
Vol 20 (17) ◽  
pp. 4181
Author(s):  
Zi-Yu Chang ◽  
Chin-Chang Chen ◽  
Hsuan-Miao Liu ◽  
Yuan-Chieh Yeh ◽  
Tung-Yi Lin ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Growth Factor ◽  
Bile Duct ◽  
Liver Fibrosis ◽  
Transforming Growth Factor ◽  
Bile Duct Ligation ◽  
Smooth Muscle Actin ◽  
Matrix Metalloproteinase 2 ◽  
Positive Effects ◽  
Duct Ligation

The purpose of this study was to investigate whether Ger-Gen-Chyn-Lian-Tang (GGCLT) suppresses oxidative stress, inflammation, and angiogenesis during experimental liver fibrosis through the hypoxia-inducible factor-1α (HIF-1α)-mediated pathway. Male C57BL/6 mice were randomly assigned to a sham-control or bile duct ligation (BDL) group with or without treatment with GGCLT at 30, 100, and 300 mg/kg. Plasma alanine aminotransferase (ALT) levels were analyzed using a diagnostic kit. Liver histopathology and hepatic status parameters were measured. Compared to control mice, the BDL mice exhibited an enlargement in liver HIF-1α levels, which was suppressed by 100 and 300 mg/kg GGCLT treatments (control: BDL: BDL + GGCLT-100: BDL + GGCLT-300 = 0.95 ± 0.07: 1.95 ± 0.12: 1.43 ± 0.05: 1.12 ± 0.10 fold; p < 0.05). GGCLT restrained the induction of hepatic hydroxyproline and malondialdehyde levels in the mice challenged with BDL, further increasing the hepatic glutathione levels. Furthermore, in response to increased hepatic inflammation and fibrogenesis, significant levels of ALT, nuclear factor kappa B, transforming growth factor-β, α-smooth muscle actin, matrix metalloproteinase-2 (MMP-2), MMP-9, and procollagen-III were found in BDL mice, which were attenuated with GGCLT. In addition, GGCLT reduced the induction of angiogenesis in the liver after BDL by inhibiting vascular endothelial growth factor (VEGF) and VEGF receptors 1 and 2. In conclusion, the anti-liver fibrosis effect of GGCLT, which suppresses hepatic oxidative stress and angiogenesis, may be dependent on an HIF-1α-mediated pathway.

Conditional loss of heparin-binding EGF-like growth factor results in enhanced liver fibrosis after bile duct ligation in mice

2013 ◽  
Vol 437 (2) ◽  
pp. 185-191 ◽  
Author(s):  
Takayo Takemura ◽  
Yuichi Yoshida ◽  
Shinichi Kiso ◽  
Takashi Kizu ◽  
Kunimaro Furuta ◽  
...  
Keyword(s):  
Growth Factor ◽  
Bile Duct ◽  
Liver Fibrosis ◽  
Bile Duct Ligation ◽  
Heparin Binding ◽  
Duct Ligation

Adenoviral CCN3/NOV gene transfer fails to mitigate liver fibrosis in an experimental bile duct ligation model because of hepatocyte apoptosis

2012 ◽  
Vol 32 (9) ◽  
pp. 1342-1353 ◽  
Author(s):  
Erawan Borkham-Kamphorst ◽  
Sebastian Huss ◽  
Eddy Leur ◽  
Ute Haas ◽  
Ralf Weiskirchen
Keyword(s):  
Bile Duct ◽  
Gene Transfer ◽  
Liver Fibrosis ◽  
Bile Duct Ligation ◽  
Hepatocyte Apoptosis ◽  
Duct Ligation

scholarly journals PAI-1 deficiency reduces liver fibrosis after bile duct ligation in mice through activation of tPA

FEBS Letters ◽  
2007 ◽  
Vol 581 (16) ◽  
pp. 3098-3104 ◽  
Author(s):  
Hongtao Wang ◽  
Yan Zhang ◽  
Robert O. Heuckeroth
Keyword(s):  
Bile Duct ◽  
Liver Fibrosis ◽  
Bile Duct Ligation ◽  
Duct Ligation ◽  
Pai 1

Piceatannol increases the expression of hepatocyte growth factor and IL-10 thereby protecting hepatocytes in thioacetamide-induced liver fibrosis

2016 ◽  
Vol 94 (7) ◽  
pp. 779-787 ◽  
Author(s):  
Hazem Abd-Elgawad ◽  
Nashwa Abu-Elsaad ◽  
Amr El-Karef ◽  
Tarek Ibrahim
Keyword(s):  
Growth Factor ◽  
Liver Fibrosis ◽  
Liver Function ◽  
Hepatocyte Growth Factor ◽  
Transforming Growth Factor ◽  
Histopathological Examination ◽  
Smooth Muscle Actin ◽  
Interleukin 10 ◽  
Hepatocyte Growth ◽  
Inflammatory Effect

Piceatannol is a polyphenolic analog of resveratrol that selectively inhibits the non-receptor tyrosine kinase-Syk. This study investigates the potential ability of piceatannol to attenuate liver fibrosis and protect hepatocytes from injury. Thioacetamide was injected in adult male mice (100 mg/kg, i.p., 3 times/week) for 8 weeks. Piceatannol (1 or 5 mg/kg per day) was administered by oral gavage during the last 4 weeks. Liver function biomarkers, tissue malondialdehyde (MDA), cytokeratin-18 (CK18), hepatocyte growth factor (HGF), and interleukin-10 (IL-10) were measured. Necroinflammation, fibrosis, expression of transforming growth factor (TGF)-β1, and α-smooth muscle actin (SMA) were scored by histopathological examination and immunohistochemistry. Obtained results showed ability of piceatannol (1 mg/kg) to restore liver function and reduce inflammation. It significantly (p < 0.001) reduced MDA, CK18, TGF-β1, and α-SMA expression, and increased HGF and IL-10. It can be concluded that piceatannol at low dose can inhibit TGF-β1 induced hepatocytes apoptosis and exerts an anti-inflammatory effect attenuating fibrosis progression.

Polyphenols from Camellia sinenesis attenuate experimental cholestasis-induced liver fibrosis in rats

2003 ◽  
Vol 285 (5) ◽  
pp. G1004-G1013 ◽  
Author(s):  
Zhi Zhong ◽  
Matthias Froh ◽  
Mark Lehnert ◽  
Robert Schoonhoven ◽  
Liu Yang ◽  
...  
Keyword(s):  
Bile Duct ◽  
Liver Fibrosis ◽  
Transforming Growth Factor ◽  
Bile Duct Ligation ◽  
Smooth Muscle Actin ◽  
Control Diet ◽  
Free Radical Scavengers ◽  
Bile Duct Proliferation ◽  
Duct Ligation ◽  
Experimental Cholestasis

Accumulation of hydrophobic bile acids during cholestasis leads to generation of oxygen free radicals in the liver. Accordingly, this study investigated whether polyphenols from green tea Camellia sinenesis, which are potent free radical scavengers, decrease hepatic injury caused by experimental cholestasis. Rats were fed a standard chow or a diet containing 0.1% polyphenolic extracts from C. sinenesis starting 3 days before bile duct ligation. After bile duct ligation, serum alanine transaminase increased to 760 U/l after 1 day in rats fed a control diet. Focal necrosis and bile duct proliferation were also observed after 1–2 days, and fibrosis developed 2–3 wk after bile duct ligation. Additionally, procollagen-α1(I) mRNA increased 30-fold 3 wk after bile duct ligation, accompanied by increased expression of α-smooth muscle actin and transforming growth factor-β and the accumulation of 4-hydroxynenonal, an end product of lipid peroxidation. Polyphenol feeding blocked or blunted all of these bile duct ligation-dependent changes by 45–73%. Together, the results indicate that cholestasis due to bile duct ligation causes liver injury by mechanisms involving oxidative stress. Polyphenols from C. sinenesis scavenge oxygen radicals and prevent activation of stellate cells, thereby minimizing liver fibrosis.

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