Suppression of transforming growth factor-β results in upregulation of transcription of regeneration factors after chronic liver injury

2004 ◽  
Vol 41 (6) ◽  
pp. 974-982 ◽  
Author(s):  
Toru Nakamura ◽  
Takato Ueno ◽  
Masaharu Sakamoto ◽  
Ryuichiro Sakata ◽  
Takuji Torimura ◽  
...  
Keyword(s):  
Growth Factor ◽  
Liver Injury ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Chronic Liver ◽  
Chronic Liver Injury

Liver fibrosis: a balance of ACEs?

2007 ◽  
Vol 113 (3) ◽  
pp. 109-118 ◽  
Author(s):  
Fiona J. Warner ◽  
John S. Lubel ◽  
Geoffrey W. McCaughan ◽  
Peter W. Angus
Keyword(s):  
Angiotensin Ii ◽  
Growth Factor ◽  
Liver Fibrosis ◽  
Liver Injury ◽  
Angiotensin Converting Enzyme ◽  
Transforming Growth Factor ◽  
Tissue Growth ◽  
Chronic Liver ◽  
Converting Enzyme ◽  
Chronic Liver Injury

There is an increasing body of evidence to suggest that the RAS (renin–angiotensin system) contributes to tissue injury and fibrosis in chronic liver disease. A number of studies have shown that components of a local hepatic RAS are up-regulated in fibrotic livers of humans and in experimental animal models. Angiotensin II, the main physiological effector molecule of this system, mediates liver fibrosis by stimulating fibroblast proliferation (myofibroblast and hepatic stellate cells), infiltration of inflammatory cells, and the release of inflammatory cytokines and growth factors such as TGF (transforming growth factor)-β1, IL (interleukin)-1β, MCP (monocyte chemoattractant protein)-1 and connective tissue growth factor. Furthermore, blockade of the RAS by ACE (angiotensin-converting enzyme) inhibitors and angiotensin type 1 receptor antagonists significantly attenuate liver fibrosis in experimental models of chronic liver injury. In 2000 ACE2 (angiotensin-converting enzyme 2), a human homologue of ACE, was identified. ACE2 efficiently degrades angiotensin II to angiotensin-(1–7), a peptide which has recently been shown to have both vasodilatory and tissue protective effects. This suggests that ACE2 and its products may be part of an alternate enzymatic pathway in the RAS, which counterbalances the generation and actions of angiotensin II, the ACE2–angiotensin-(1–7)–Mas axis. This review focuses on the potential roles of the RAS, angiotensin II and ACE2 in chronic liver injury and fibrogenesis.

scholarly journals α2-Adrenergic Receptor in Liver Fibrosis: Implications for the Adrenoblocker Mesedin

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 456 ◽  
Author(s):  
Ute A. Schwinghammer ◽  
Magda M. Melkonyan ◽  
Lilit Hunanyan ◽  
Roman Tremmel ◽  
Ralf Weiskirchen ◽  
...  
Keyword(s):  
Growth Factor ◽  
Liver Fibrosis ◽  
Liver Injury ◽  
Transforming Growth Factor ◽  
Smooth Muscle Actin ◽  
Transforming Growth Factor Β ◽  
Liver Sinusoidal Endothelial Cells ◽  
Mediated Effects ◽  
Liver Sinusoids ◽  
Endothelial Nitric Oxide

The noradrenergic system is proposed to play a prominent role in the pathogenesis of liver fibrosis. While α1- and β-adrenergic receptors (ARs) are suggested to be involved in a multitude of profibrogenic actions, little is known about α2-AR-mediated effects and their expression pattern during liver fibrosis and cirrhosis. We explored the expression of α2-AR in two models of experimental liver fibrosis. We further evaluated the capacity of the α2-AR blocker mesedin to deactivate hepatic stellate cells (HSCs) and to increase the permeability of human liver sinusoidal endothelial cells (hLSECs). The mRNA of α2a-, α2b-, and α2c-AR subtypes was uniformly upregulated in carbon tetrachloride-treated mice vs the controls, while in bile duct-ligated mice, only α2b-AR increased in response to liver injury. In murine HSCs, mesedin led to a decrease in α-smooth muscle actin, transforming growth factor-β and α2a-AR expression, which was indicated by RT-qPCR, immunocytochemistry, and Western blot analyses. In a hLSEC line, an increased expression of endothelial nitric oxide synthase was detected along with downregulated transforming growth factor-β. In conclusion, we suggest that the α2-AR blockade alleviates the activation of HSCs and may increase the permeability of liver sinusoids during liver injury.

scholarly journals Platelet-derived growth factor isoform expression in carbon tetrachloride-induced chronic liver injury

2008 ◽  
Vol 88 (10) ◽  
pp. 1090-1100 ◽  
Author(s):  
Erawan Borkham-Kamphorst ◽  
Evgenia Kovalenko ◽  
Claudia R C van Roeyen ◽  
Nikolaus Gassler ◽  
Michael Bomble ◽  
...  
Keyword(s):  
Carbon Tetrachloride ◽  
Growth Factor ◽  
Liver Injury ◽  
Chronic Liver ◽  
Platelet Derived Growth Factor ◽  
Chronic Liver Injury ◽  
Isoform Expression

scholarly journals Characterization of Growth-Differentiation Factor 15, a Transforming Growth Factor β Superfamily Member Induced following Liver Injury

2000 ◽  
Vol 20 (10) ◽  
pp. 3742-3751 ◽  
Author(s):  
Edward C. Hsiao ◽  
Leonidas G. Koniaris ◽  
Teresa Zimmers-Koniaris ◽  
Suzanne M. Sebald ◽  
Thanh V. Huynh ◽  
...  
Keyword(s):  
Carbon Tetrachloride ◽  
Growth Factor ◽  
Liver Injury ◽  
Transforming Growth Factor ◽  
Experimental Treatment ◽  
Inflammatory Cells ◽  
Transforming Growth Factor Β ◽  
Northern Analysis ◽  
Growth Differentiation Factor 15 ◽  
Differentiation Factor

ABSTRACT We have identified a new murine transforming growth factor β superfamily member, growth-differentiation factor 15 (Gdf15), that is expressed at highest levels in adult liver. As determined by Northern analysis, the expression ofGdf15 in liver was rapidly and dramatically up-regulated following various surgical and chemical treatments that cause acute liver injury and regeneration. In situ hybridization analysis revealed distinct patterns of Gdf15 mRNA localization that appeared to reflect the known patterns of hepatocyte injury in each experimental treatment. In addition, treatment of two hepatocyte-like cell lines with either carbon tetrachloride or heat shock inducedGdf15 mRNA expression, indicating that direct cellular injury can induce Gdf15 expression in the absence of other cell types, such as inflammatory cells. In order to investigate the potential functions of Gdf15, we created Gdf15 null mice by gene targeting. Homozygous null mice were viable and fertile. Despite the dramatic regulation of Gdf15 expression observed in the partial-hepatectomy and carbon tetrachloride injury models, we found no differences in the injury responses between homozygous null mutants and wild-type mice. Our findings suggest either that Gdf15 does not have a regulatory role in liver injury and regeneration or that Gdf15 function within the liver is redundant with that of other signaling molecules.

Characterization of Growth-Differentiation Factor 15, a Transforming Growth Factor β Superfamily Member Induced following Liver Injury

2000 ◽  
Vol 20 (10) ◽  
pp. 3742-3751
Author(s):  
Edward C. Hsiao ◽  
Leonidas G. Koniaris ◽  
Teresa Zimmers-Koniaris ◽  
Suzanne M. Sebald ◽  
Thanh V. Huynh ◽  
...  
Keyword(s):  
Growth Factor ◽  
Liver Injury ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Growth Differentiation Factor 15 ◽  
Differentiation Factor

scholarly journals Hepatoprotective Effect of the Fruits of Polygonum orientale L. Against Carbon Tetrachloride-Induced Liver Fibrosis in Mice

2020 ◽  
Vol 15 (11) ◽  
pp. 1934578X2097150
Author(s):  
Yung-Jia Chiu ◽  
Kun-Chang Wu ◽  
Jen-Chieh Tsai ◽  
Chun-Pin Kao ◽  
Jung Chao ◽  
...  
Keyword(s):  
Carbon Tetrachloride ◽  
Growth Factor ◽  
Liver Injury ◽  
Transforming Growth Factor ◽  
Smooth Muscle Actin ◽  
Transforming Growth Factor Β ◽  
Serum Levels ◽  
Hepatoprotective Activity ◽  
Tissue Growth ◽  
Factor Α

The aim of this study was to evaluate the hepatoprotective effects of the fruits of Polygonum orientale L. (POE) against fibrosis in carbon tetrachloride (CCl4)-induced liver injury. Bioactive components of POE were identified using liquid chromatography (LC)-mass spectrometry (MS)/MS by comparison with standards. Treatment with either silymarin (200 mg/kg) or POE (0.5 and 1.0 g/kg) caused significant decreases in the serum levels of enzymes and reduced the extent of liver lesions and fibrosis in histological analysis. POE (0.5 and 1.0 g/kg) decreased the levels of malondialdehyde, nitric oxide, proinflammatory cytokines (ie, tumor necrosis factor-α, interleukin [IL]-1β, and IL-6), an inflammatory cytokine (ie, cyclooxygenase-2), a profibrotic cytokine (ie, transforming growth factor-β), and fibrosis-related proteins (ie, connective tissue growth factor and α-smooth muscle actin) in the liver and enhanced the activities of the antioxidative enzymes superoxide dismutase, glutathione peroxidase, glutathione reductase, and catalase. Quantitative analysis of the active constituents in POE revealed an extract composition of 3.4 mg/g of protocatechuic acid, 20.8 mg/g of taxifolin, and 5.6 mg/g of quercetin. We have demonstrated that the hepatoprotective mechanisms of POE are likely to be associated with the decrease in inflammatory cytokines by increasing the activities of antioxidant enzymes. Our findings provide evidence that POE possesses a hepatoprotective activity to ameliorate chronic liver injury.

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