الفهرس 
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Abstract
Liver fibrosis is a common wound healing response to chronic liver injury of all causes (e.g., alcohol, hepatitis B and C viruses, nonalcoholic fatty liver disease, etc.).
Fibrosis results from prolonged parenchymal cell apoptosis and necrosis associated with an inflammatory reaction that leads to recruitment of immune cells, activation and accumulation of fibrogenic cells, and extracellular matrix accumulation.
The fibrogenic process is driven by hepatic myofibroblasts, that mainly derived from hepatic stellate cells undergoing a transdifferentiation in response to paracrine/autocrine signals produced by neighboring inflammatory and parenchymal cells.
Progression of fibrosis upon sustained liver insult is associated with expansion of fibrotic septa, ultimately leading to cirrhosis which is regarded as a high public health burden worldwide, representing the most common nonneoplastic cause of death among diseases of the gastrointestinal tract worldwide Therefore, efficient antifibrotic therapeutic approaches are a high priority goal.
Hepatocyte growth factor has been used for gene therapy of liver fibrosis due to its well-known anti-fibrotic effect in animal models of fibrosis. As HGF can suppress the expression of TGFβ the most potent fibrogenic factor, inhibiting its downstream signaling pathway , induce collagenase expression to remodel ECM and it can induce HSC apoptosis.
The goal of this study is to enhance resolution of liver fibrosis and to prevent liver failure through the transfer of HGF.
In our study, rats received intraperitonial injection of carbon tetrachloride (CCl4) to induce fibrosis then the rats were divided into 3 groups. Group A was injected with adenovirus vectors encoding HGF. Group B was injected by saline and serve as positive control. Group C received saline to serve as negative (healthy) control.
The fibrosed liver tissue was analyzed to detect adenoviral vector gene in tissues (Adenovirus E4) by PCR and to confirm HGF overexpression in the liver through detection of HGF by RT-PCR and detection of HGF protein by ELISA, to study the effect of HGF gene transfer on fibrotic markers as (rat TIMP-1, rat TGFβ-1, rat SMA , rat PPAR, rat Col1A1 genes) by RT-PCR and finally to study HGF effect on both ASH1and EZH2 proteins by slot blot technique .
Also the histopathological changes (PCNA, collagen area percent) were measured in liver tissue sections by immunohistochemistry and by Sirius red staining, respectively.
Our results showed that group A (which was treated by HGF) has significant reduction of fibrosis both at the transcriptional level, fibrosis parameters and finally by the histopathological evaluation.
We concluded that administration of adenovector encoding HGF is effective in the resolution of CCl4-induced fibrosis in rats.