Plasmid Diliverded ShRNA Knocking Down CTGF In Rat Hepatic Stellate Cells

Background/Objective Liver fibrosis is characterized by an excessive accumula- tion of extracellular matrix components in the parenchyma. It is a major complication of chronic liver diseases such as viral hepatitis or alcoholic liver disease. Progression of fibrosis to cirrhosis entails a high rate of morbidity and carries the risk of hepato- cellular carcinoma development. At this time, there is no specific antifibrotic therapy available except the etiologic treatment of the causative diseases. Despite the thera- peutic improvement, especially in viral hepatitis B treatment, fibrosis progression remains a serious issue in many patients. Therefore, therapeutics specifically aimed at decreasing fibrogenesis is desirable. Extracellular matrix deposition results from the activity of fibrogenic cells. Liver fibrogenic cells are myofibroblasts that derive from the activation of precursor cells, i.e., hepatic stellate cells (HSC) and portal fibroblasts. The functions of fibrogenic cells are controlled by many growth factors and cytokines. Transforming growth factor (TGF) - β1 has been shown to be involved at all steps of liver fibrogenesis. It contributes to HSC activation, increases extracellular matrix synthesis, and up-regulates the expression of inhibitors of extracellular matrix breakdown. Various approaches to TGF-β1 antagonism have shown some success in experimental liver fibrogenesis. However, given the wide range of action of TGF-β1 in addition to fibrogenesis, the safety of this option in the long term remains unknown. Among the molecules regulated by TGF-β1, connective...