Hepatic cellular microenvironment:a novel drug target for anti-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.Keywords:
Hepatic stellate cell
Hepatic fibrosis
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Hepatic stellate cell
Hepatic fibrosis
Steatohepatitis
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Hepatic stellate cell
Hepatic fibrosis
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Hepatic stellate cell
Hepatic fibrosis
Surgical oncology
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Hepatic fibrosis is a dynamic reversible process.It is hotspots to develop drugs which can suppress even reverse liver fibrosis in the treatment of chronic liver disease.The current progress of anti-hepatic fibrosis drug research was reviewed based on the important part in fibrosis process from different drug targets,such as the liver cells,hepatic stellate cells and extracellular matrix.
Hepatic fibrosis
Hepatic stellate cell
Chronic liver disease
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Hepatic fibrosis is a complex mechanism defined by the net deposition of the extracellular matrix (ECM) owing to liver injury caused by multiple etiologies such as viral hepatitis and nonalcoholic fatty liver disease. Many cell types are implicated in liver fibrosis development and progression. In general, liver fibrosis starts with the recruitment of inflammatory immune cells to generate cytokines, growth factors, and other activator molecules. Such chemical mediators drive the hepatic stellate cells (HSCs) to activate the production of the ECM component. The activation of HSC is thus a crucial event in the fibrosis initiation, and a significant contributor to collagen deposition (specifically type I). This review explores the causes and mechanisms of hepatic fibrosis and focuses on the roles of key molecules involved in liver fibro genesis, some of which are potential targets for therapeutics to hamper liver fibro genesis.
Hepatic stellate cell
Hepatic fibrosis
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Hepatic fibrosis is a dynamic process that occurs as a wound healing response against liver injury. During fibrosis, crosstalk between parenchymal and non-parenchymal cells, activation of different immune cells and signaling pathways, as well as a release of several inflammatory mediators take place, resulting in inflammation. Excessive inflammation drives hepatic stellate cell (HSC) activation, which then encounters various morphological and functional changes before transforming into proliferative and extracellular matrix (ECM)-producing myofibroblasts. Finally, enormous ECM accumulation interferes with hepatic function and leads to liver failure. To overcome this condition, several therapeutic approaches have been developed to inhibit inflammatory responses, HSC proliferation and activation. Preclinical studies also suggest several targets for the development of anti-fibrotic therapies; however, very few advanced to clinical trials. The pathophysiology of hepatic fibrosis is extremely complex and requires comprehensive understanding to identify effective therapeutic targets; therefore, in this review, we focus on the various cellular and molecular mechanisms associated with the pathophysiology of hepatic fibrosis and discuss potential strategies to control or reverse the fibrosis.
Hepatic stellate cell
Hepatic fibrosis
Myofibroblast
Crosstalk
Pathophysiology
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Hepatic stellate cell
Hepatic fibrosis
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This recent progress in the research of anti-fibrotic drugs in recent years was reviewed.Hepatic fibrosis,resulted from sustained chronic liver injuries,is a pathological change characterized by the excessive accumulation of extracellular matrix(ECM) including collagen and other ECM components and characterized by the tissue structure reconstruction,in which the activation of hepatic stellate cells(HSCs)plays a pivotal role.Continuous clarification of molecular mechanisms has witnessed tremendous progress in the research and development of hepatic anti-fibrotic drugs covering hepatocyte protective agent,ECM synthesis and degradation modulator,HSCs activation and apoptosis modulator,anti-inflammatory agent and immunomodulator,and traditional Chinese medicine in treating hepatic fibrosis has also achieved some progress.
Hepatic stellate cell
Hepatic fibrosis
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Hepatic fibrosis is a wound healing response to chronic liver injury. The most characteristic feature of hepatic fibrosis is the excessive deposition of extracellular matrix (ECM) in liver. It is well known that the activation of hepatic stellate cells (HSCs) is the key event in the process of hepatic fibrosis. Fibrogenic cells,cytokines,growth factors,enzymes, and their inhibitors play a pivotal role in fibrogenesis.These will advance our recognition for pathogenic mechanisms of hepatic fibrosis.
Hepatic stellate cell
Hepatic fibrosis
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The activation of hepatic stellate cells ( HSCs) is the key step for liver fibrogenesis and progression. Increasing clinical and experimental studies suggest that hepatic fibrosis is reversible. One of the major manifestations for reduction of fibrosis is the decrease of activated HSCs. Thus,how to clear the activated hepatic stellate cells has become a focus of study on treatment of hepatic fibrosis. By now there have been two potential pathways for reduction of activated HSCs:reversal of the phenotype of HSCs and apoptosis. This paper reviews the anti-hepatic fibrosis strategies based on the clearance of activated HSCs.
Hepatic stellate cell
Hepatic fibrosis
Chronic liver disease
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