Enhanced hepatic collagen type I mRNA expression into fat-storing cells in a rodent model of hemochromatosis†
Antonello PietrangeloRossana GualdiG. CasalgrandiAlbert GeertsPieter De BleserGiuliana MontosiEzio Ventura
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Abstract:
In recent years, identifying the hepatic cell type responsible for collagen synthesis in experimental models of postnecrotic or inflammatory fibrosis has been the subject of active investigation. In primary iron overload states, however, hepatic fibrosis and cirrhosis occur without accompanying necroinflammatory phenomena. In this study, we combined morphological, immunological, cell isolation and purification and molecular biological techniques to identify the hepatic cell responsible for enhanced collagen type I gene expression during chronic enteral iron overload in the rat. Ultrastructural analysis of liver tissue sections from iron-loaded rats specifically revealed an altered appearance of fat-storing cells, which showed few if any fat droplets left and increased rough endoplasmic reticulum. In situ hybridization analysis with specific complementary RNA probes identified enhanced signal for collagen type I into nonparenchymal cells in zones 1 and 2, without signal over the background onto iron-laden hepatocytes. Immunocytochemistry with desmin antibodies combined with in situ hybridization on the same tissue sections identified the cells expressing high level of collagen type I transcripts as fat-storing cells. Northern-blot analysis on RNA extracted from various purified cell isolates, confirmed the presence of collagen type I mRNA signal only into the fat-storing cells isolate. Our study shows that in an experimental model of metabolic fibrosis in which the hepatotoxin selectively accumulates into parenchymal cells, fat-storing cells are the main source of enhanced collagen type I gene expression. (Hepatology 1994;19:714-721).Keywords:
Hepatic stellate cell
Cell type
Hepatic fibrosis
Type I collagen
Northern blot
Hepatic fibrosis is an essential pathological process involved in various chronic hepatic diseases that may deteriorate into hepatic cirrhosis and hepatic cancer.Thus,it has become hot topics to seek bioactive components against hepatic fibrosis.Many researches found that saponins from Panax notoginseng have the potential to be a bioactive agent against hepatic fibrosis.This review summarizes the research findings that saponins from Panax notoginseng showed a protection of hepatic cells from the fibrosis by inhibition of hepatic stellate cells and synthesis of extracellular matrix,promoting apoptosis of hepatic stellate cells and degradation of extracellular matrix.The prospects of saponins from Panax notoginseng in management of hepatic fibrosis are also elaborated.
Panax notoginseng
Hepatic stellate cell
Hepatic fibrosis
Chronic hepatic
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Liver fibrosis is considered as a serious disease,which can lead to portal hypertension,liver cirrhosis and liver failure.It has been well established that the activation of hepatic stellate cells plays a vital role in the hepatic fibrosis.Inhibiting hepatic stellate cells activation and accelerating clearance of hepatic stellate cells are promising strategies against liver fibrosis.In this assay,apoptosis,senescence and the clearance of the activated hepatic stellate cells will be reviewed,which aims to demonstrate the effect of hepatic stellate cells and its mechanism in hepatic fibrosis regression.
Hepatic stellate cell
Hepatic fibrosis
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Hepatic stellate cell
Hepatic fibrosis
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Transforming growth factor-β1 (TGF-β1) is the strongest hepatic fibrosis promoter. It can inhibit the proliferation of hepatic cells, endothelial cells and epithelial cells, promote the synthesis of extracellular matrix (ECM), induce the apoptosis of hepatic cells, and promote the activation of hepatic stellate cells (HSC). Knowing the mechanism how TGF-β1 causes hepatic fibrosis has significance in the diagnosis and treatment of hepatic fibrosis.
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Transforming growth factor-β1; Hepatic fibrosis; Extracellular matrix; Hepatic stellate cells
Hepatic stellate cell
Hepatic fibrosis
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Hepatic fibrosis is the accumulation of excess collagen as a result of chronic liver injury. If left unabated, hepatic fibrosis can lead to the disruption of the liver architecture, portal hypertension, and increased risk of progression to cirrhosis and hepatocellular carcinoma. The thiazolidinedione class of antidiabetic drugs, through their target peroxisome proliferator-activated receptor γ (PPARγ), have protective effects against liver fibrosis, and can inhibit the profibrotic activity of hepatic stellate cells, the major collagen-producing liver cells. However, these drugs have been ineffective in the treatment of established fibrosis, possibly due to side effects such as increased weight and adiposity. Recently, selective PPARγ modulators that lack these side effects have been identified, but their role in treating fibrosis has not been studied. In this study, we tested the effectiveness of one of these selective modulators, SR1664, in the mouse carbon tetrachloride model of established hepatic fibrosis. Treatment with SR1664 reduced the total and type 1 collagen content without increasing body weight. The abundance of activated hepatic stellate cells was also significantly decreased. Finally, SR1664 inhibited the profibrotic phenotype of hepatic stellate cells. In summary, a selective PPARγ modulator was effective in the reduction of established hepatic fibrosis and the activated phenotype of hepatic stellate cells. This may represent a new treatment approach for hepatic fibrosis.
Hepatic stellate cell
Hepatic fibrosis
Thiazolidinedione
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Hepatic stellate cell(HSC),with a variety of physiological functions,is a kind of liver stromal cell.It plays an important role in the formation and regulation of hepatic fibrosis.HSC also plays a key role in hepatic fibrosis in schistosomiasis.This review focused on biological characteristics,activation of hepatic stellate cells and its role in hepatic fibrosis in schistosomiasis.
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Hepatic stellate cell; Schistosomiasis; Hepatic fibrosis; Regulation
Hepatic stellate cell
Hepatic fibrosis
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Abstract Liver cirrhosis is a leading cause of death from liver‐related diseases accompanied by a variety of complications; however, hepatic fibrosis, an inevitable stage of cirrhosis, is possible to be reversed and cured. Hepatic stellate cells (HSCs) are the primary cells that secrete extracellular matrix in the liver and play a dominant role in the pathogenesis of hepatic fibrosis. Effective therapeutic approaches for reversing hepatic fibrosis aim at inhibiting the activation of HSCs and inducing their inactivation or death. This review highlights the mechanism by which traditional Chinese medicine (TCM) regulates the activity of HSCs and exerts antifibrotic effects, providing insights and prospects for the treatment of hepatic fibrosis with TCM.
Hepatic stellate cell
Hepatic fibrosis
Pathogenesis
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Abstract Background: Activated hepatic stellate cells are the most critical cell responsible for liver fibrosis. In liver fibrogenesis, platelet-derived growth factor is the most prominent mitogen for hepatic stellate cells. This study aims to explore the potential of gadolinium (Gd)-labeled cyclic peptides (pPB) targeted to platelet-derived growth factor receptor-β (PDGFR-β) as a magnetic resonance imaging (MRI) radiotracer to identify the progress of liver fibrosis by imaging hepatic PDGFR-β expression. Results: Hepatic PDGFR-β expression level was found to be paralleled with the severity of liver fibrosis, which was increased with the progression of fibrosis and reduced with the regression. Majority of cells expressing PDGFR-β was determined to be activated hepatic stellate cells in fibrotic livers. Culture-activated human hepatic stellate cells expressed abundant PDGFR-β, and FITC-labeled pPB could bind to human hepatic stellate cells in a concentration and time dependent manner. With Gd-labeled pPB as a tracer, an MRI modality demonstrated that the relative hepatic T1-weighed MR signal value was increased progressively along with severity of hepatic fibrosis and reduced with the remission. Conclusion: Hepatic PDGFR-β expression reflects the progress of hepatic fibrosis, and MR imaging using Gd-labeled pPB as a tracer may distinguish different stages of liver fibrosis in mice.
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Hepatic fibrosis
Platelet-derived growth factor
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Hepatic stellate cell
Hepatic fibrosis
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To screen anti-hepatic fibrosis drugs,the relationship between hepatocellular microenvironment and hepatic fibrosis is analyzed and focused on hepatic stellate cells in this paper.Hepatocellular microenvironment is composed of hepatic stellate cells,extracellular matrix,matrix metalloproteinases,Kupffer cells and natural killer cells.Hepatic fibrosis is induced by the imbalance among the parts of hepatocellular microenvironment.So hepatocellular microenvironment should be a complex drug target for the treatment of hepatic fibrosis,and be applied to screen tranditional ethno drugs,which has the advantages of multi-target and multi-mechanism on diseases,to develop innovative anti-fibrotic drugs.
Hepatic stellate cell
Hepatic fibrosis
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