Home About us Contact
|
Home About us Contact | ||
|
|
||
Hepatic Stellate Cell Activation (hepatic + stellate_cell_activation)
Selected AbstractsUpregulation of the tumor suppressor gene menin in hepatocellular carcinomas and its significance in fibrogenesis,HEPATOLOGY, Issue 5 2006Pierre J. Zindy The molecular mechanisms underlying the progression of cirrhosis toward hepatocellular carcinoma were investigated by a combination of DNA microarray analysis and literature data mining. By using a microarray screening of suppression subtractive hybridization cDNA libraries, we first analyzed genes differentially expressed in tumor and nontumor livers with cirrhosis from 15 patients with hepatocellular carcinomas. Seventy-four genes were similarly recovered in tumor (57.8% of differentially expressed genes) and adjacent nontumor tissues (64% of differentially expressed genes) compared with histologically normal livers. Gene ontology analyses revealed that downregulated genes (n = 35) were mostly associated with hepatic functions. Upregulated genes (n = 39) included both known genes associated with extracellular matrix remodeling, cell communication, metabolism, and post-transcriptional regulation gene (e.g., ZFP36L1), as well as the tumor suppressor gene menin (multiple endocrine neoplasia type 1; MEN1). MEN1 was further identified as an important node of a regulatory network graph that integrated array data with array-independent literature mining. Upregulation of MEN1 in tumor was confirmed in an independent set of samples and associated with tumor size (P = .016). In the underlying liver with cirrhosis, increased steady-state MEN1 mRNA levels were correlated with those of collagen ,2(I) mRNA (P < .01). In addition, MEN1 expression was associated with hepatic stellate cell activation during fibrogenesis and involved in transforming growth factor beta (TGF-,),dependent collagen ,2(I) regulation. In conclusion, menin is a key regulator of gene networks that are activated in fibrogenesis associated with hepatocellular carcinoma through the modulation of TGF-, response. (HEPATOLOGY 2006;44:1296,1307.) [source] Immunopathogenesis of hepatitis C virus infection and hepatic fibrosis: New insights into antifibrotic therapy in chronic hepatitis CHEPATOLOGY RESEARCH, Issue 8 2007Rosāngela Teixeira Fibrosis and cirrhosis represent the consequences of a sustained wound-healing response to chronic liver injury of any cause. Chronic hepatitis C virus (HCV) has emerged as a leading cause of cirrhosis in the USA and throughout the world. HCV may induce fibrogenesis directly by hepatic stellate cell activation or indirectly by promoting oxidative stress and apoptosis of infected cells. The ultimate result of chronic HCV injury is the accumulation of extracellular matrix with high density type I collagen within the subendothelial space of Disse, culminating in cirrhosis with hepatocellular dysfunction. The treatment of hepatitis C with the combination of pegylated interferon and ribavirin is still both problematic and costly, has suboptimal efficacy, serious side effects and a high level of intolerance, and is contraindicated in many patients. Hence, new approaches have assumed greater importance, for which there is an urgent need. The sustained progress in understanding the pathophysiology of hepatic fibrosis in the past two decades has increased the possibility of developing drugs specifically targeting the fibrogenic process. Future efforts should identify genetic markers associated with fibrosis risk in order to tailor the treatment of HCV infection based on genetically regulated pathways of injury and/or fibrosis. Such advances will expand the arsenal to overcome liver fibrosis, particularly in patients with hepatic diseases who have limited treatment options, such as those patients with chronic hepatitis C who have a high risk of fibrosis progression and recurrent HCV disease after liver transplantation. [source] Oxidative stress: Does it ,initiate' hepatic stellate cell activation or only ,perpetuate' the process?JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 10 2002Minoti Apte First page of article [source] The Ethanol-soluble Part of a Hot-water Extract from Artemisia iwayomogi Inhibits Liver Fibrosis Induced by Carbon Tetrachloride in RatsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 7 2000EUN-JEON PARK This study was carried out to investigate the protective effects of the hot-water extract from Artemisia iwayomogi (Compositae) on carbon tetrachloride-induced liver fibrosis in rats. Liver injury was induced by oral administration of carbon tetrachloride (1 mL kg,1) twice a week during 4 weeks of A. iwayomogi treatment. Extracts from A. iwayomogi were prepared and administered to rats orally (2 g kg,1 as A. iwayomogi for 4 weeks) as follows: group 1, hot-water extract; group 2, ethanol-soluble part of hot-water extract; group 3, ethanol-insoluble part of hot-water extract; and group 4, methanol extract. In rats treated with the ethanol-soluble part of the hot-water extract, liver hydroxyproline content was reduced to 74% that of carbon tetrachloride control rats (P < 0.05). Protein expression of alpha smooth muscle cell like actin was also decreased in rats treated with the ethanol-soluble part of the hot-water extract, which indicates inhibition of hepatic stellate cell activation. Liver malondialdehyde levels were significantly lowered in rats treated with the ethanol-soluble part of hot-water extract (P < 0.05). Serum cholesterol levels in rats treated with hot-water extract, ethanol-soluble or -insoluble parts of hot-water extract or methanol extract were significantly reduced when compared with those of carbon tetrachloride control rats (P < 0.05). The ethanol-soluble part of the hot-water extract from A. iwayomogi inhibited fibrosis and lipid peroxidation in rats with liver fibrosis induced by carbon tetrachloride. Both hot-water extract (either ethanol-soluble or -insoluble) and methanol extract of A. iwayomogi also lowered serum cholesterol levels in fibrotic rats. [source] | ||||||||||