Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tenascin is an oligomeric glycoprotein of the extracellular matrix synthesized during embryonic development. It is prominently expressed in a variety of tumors. The role of tenascin in liver tissue is, however, unknown. We used immunocytochemistry to define the localization of tenascin and compare this with the localization of non-collagenous proteins, such as laminin and fibronectin, in normal human liver and pathological liver from patients with chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. In normal liver, tenascin expression was localized along the sinusoidal and vascular wall. In fibrotic liver, tenascin was also observed in the region between the hepatic parenchyma and the fibrosing portal tracts, especially in areas of piecemeal necrosis in chronic hepatitis. Immuno-EM study of liver tissue in chronic hepatitis strongly suggested the synthesis and secretion of tenascin by fat-storing cells into the space of Disse. In hepatocellular carcinoma, tenascin was expressed in both the capsule and lobular septa, but not in the sinusoidal walls of the tumors. These results led us to postulate a close relationship between the occurrence of this protein and disease processes such as fibrosis and cancer invasion.
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PMID:Tenascin expression in human chronic liver disease and in hepatocellular carcinoma. 137 63

To evaluate the diagnostic significance of tenascin, the extracellular matrix glycoprotein in chronic liver disease, serum tenascin levels were measured by a newly developed ELISA in 21 patients with chronic persistent hepatitis, in 55 with chronic active hepatitis, in 59 with liver cirrhosis, in 31 with hepatocellular carcinoma, in 26 with acute hepatitis and in 66 healthy subjects. The serum tenascin level was significantly elevated in the patients with chronic active hepatitis, liver cirrhosis, hepatocellular carcinoma, and acute hepatitis when compared with the healthy subjects (p < 0.001). The serum tenascin level also increased with increasing severity of chronic liver diseases. A significant correlation was observed between the serum tenascin levels and serum levels of various extracellular matrix proteins such as type III procollagen N-aminoterminal peptide (PIIIP), laminin and the 7S domain of type IV collagen (p < 0.001). A strong positive correlation was observed between the serum tenascin levels and histologic findings, particularly in the degree of hepatic fibrosis. This is the first report documenting serum tenascin level increases in patients with various chronic liver diseases. The measurement of the serum tenascin levels may provide additional information relevant to the study of connective tissue.
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PMID:Serum tenascin levels in chronic liver disease. 752 6

The extracellular matrix (ECM) located in and around tumors is different from normal organ stroma, and there is evidence that it is critically involved in carcinogenesis and malignant growth. Whereas an abnormal composition of ECM in hepatocellular carcinomas (HCC's) has previously been demonstrated, not much is known so far with respect to putative HCC precursor lesions. We have, therefore, systematically analyzed the immunohistochemical reactivity for two major ECM components, tenascin and type IV collagen, in three types of liver cell dysplasia (LCD), and compared the findings with patterns observed in HCC's of different types and grades. Tenascin reactivity was generally stronger in HCC's than in cirrhosis. In cirrhotic nodules harboring areas of LCD, tenascin expression was significantly lower in small cell LCD than in large cell LCD. Type IV collagen reactivity in and around HCC's decreased as a function of a lower differentiation grade. In both groups of cirrhosis, i.e. with or without HCC, cirrhotic nodules occupied by the small cell variant of LCD exhibited a significantly lower type IV collagen reactivity than those with large cell LCD or simple regenerative cells. Taken together these findings suggest that, similar to adenomatous hyperplasia, small cell LCD is characterized by an abnormal tenascin and type IV collagen expression, thus reflecting the defective ECM pattern observed in HCC's.
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PMID:Tenascin and type IV collagen expression in liver cell dysplasia and in hepatocellular carcinoma. 886 54

The aim of this study was to follow semiquantitatively by immunohistochemical means the alterations of the expression of the hepatic glycoproteins tenascin, fibronectin, and laminin in two different models of chronic liver injury, i.e. thioacetamide-induced liver cirrhosis and fibrosis after bile duct ligation. The tenascin distribution pattern observed during cholostasis-induced liver fibrosis showed some similarities, but also some differences in comparison with the results obtained after TAA intoxication. Most importantly, the data show that tenascin staining was detectable in almost all areas of the chronically injured livers up to 3 and 6 months in bile duct-ligated and chemically-injured livers, respectively. Thus, tenascin does not seem to play only a transient role in the fibrogenetic process as previously suggested. Laminin was strongly stained in proliferating ductules, whereas only a weak continuous distribution was observed along the sinusoidal wall. Furthermore, our findings confirm the role of fibronectin as a pacemaker of fibrosis. Regional differences in the kinetics of the expression of the glycoproteins may reflect local differences in their production by parenchymal or non parenchymal cells or regional patterns of proteolytic activity.
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PMID:Expression of tenascin, fibronectin, and laminin in rat liver fibrogenesis--a comparative immunohistochemical study with two models of liver injury. 978 3

Excessive consumption of alcoholic beverages may be associated with gastrointestinal symptoms, including dyspepsia and diarrhoea. It is not clear whether or not chronic alcohol ingestion damages the mucosa of the small intestine. We investigated the effect of chronic alcohol abuse on the duodenal mucosa, and particularly on its extracellular matrix (ECM) network. Duodenal biopsy specimens were obtained during upper gastrointestinal endoscopy from 50 chronic alcoholics without cirrhosis and 10 healthy subjects. Morphological studies were performed by routine histology, immunohistochemistry and electron microscopy. Morphometry of duodenal tissues was performed with a computerized image analyser. No significant duodenal epithelial changes were found in alcoholics, despite an evident reduction in the enterocyte turnover. Myofibroblast-like cells were significantly increased in the villus stroma of alcoholics in comparison to controls. These cells stained positively for desmin, alpha-smooth muscle actin and for several ECM components. In alcohol abusers the thickness of the mucosal basement membrane was greater and the staining for collagen I and III was enhanced both in the basement membrane and in the villus stroma. A higher expression of tenascin was also seen at the base of villi of alcoholics. Chronic alcohol abuse may induce fibrosis of duodenal villi which is associated with a transformation of villus juxta-parenchymal cells into active subepithelial myofibroblast-like cells able to produce different ECM components.
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PMID:Ethanol-induced alterations of matrix network in the duodenal mucosa of chronic alcohol abusers. 1007 Dec 47

Transforming growth factor (TGF-beta) is the protein playing a principal role in the intracellular signalling. The most important function is ability to stimulate synthesis of extracellular matrix proteins, what is responsible for wound formation and tissue reconstruction. The damage of hepatocytes is a signal for macrophages and platelets activation, resulting in release of TGF-beta and over-expression of genes responsible for morphologic and functional changes in Ito cells. They undergo transformation into myofibroblasts and become the source of extracellular matrix proteins, such as: collagens, fibronectin, laminin, entactin, tenascin, undulin. The consequence of their accumulation in the space of Disse and inside hepatic lobuli is fibrosis, which is the form of tissue healing in the place of necrosis. However continuous action of damaging agent leads to massive fibrosis and reconstruction of liver, what is clinically manifested as cirrhosis. The role of transforming growth factor beta in the pathogenesis of liver diseases and its possible use as an indicator of disease progression were discussed in this paper.
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PMID:[Transforming growth factor beta in pathogenesis of liver diseases]. 1114 21

Vitronectin (Vn) is a multifunctional plasma glycoprotein produced by hepatocytes. Vn has been studied extensively as a cell adhesion molecule. However, its localization in the hepatic extracellular matrix has received relatively little attention. Cryosections of 5 normal liver samples and of 20 specimens showing posthepatitic cirrhosis were stained by the avidin-biotin complex method with a well-characterized monoclonal antibody to Vn. The extent and intensity of immunostaining were assessed semiquantitatively (0, no staining; 1+, weak focal staining; 2+, strong focal staining; 3+, strong diffuse staining). Paraffin sections from the same samples were stained with Masson trichrome (MT) and Shikata orcein (Or) methods. Frozen samples from selected cases were analyzed by Western blotting. In the normal liver, 3+ staining was limited to portal vessels. The portal tract connective tissue showed minimal staining (0 to 1+). Cirrhotic septa showed strong staining (2+). Septa lacking significant inflammation and composed of dense connective tissue, as indicated by MT and Or stains, showed the strongest Vn reactions (3+). Immunoblotting data strongly correlated with Vn increase in cirrhotic livers. Vn immunoreactivity is markedly increased in the cirrhotic liver matrix, regardless of the documented decrease in plasma Vn. Binding to collagen, elastin, and proteoglycans is the current favored mechanism of Vn deposition in tissues. Previous studies in cirrhotic patients showed increased affinity of plasma Vn to collagen. Vn is also increased in aged skin, associated with dermal elastic fibers. In other tissues, Vn deposition reflects chronicity of injury. Therefore, Vn immunoreactivity in liver can be considered a marker of fibrosis, especially of chronic/mature fibrosis, paralleling previous observations on enhanced orcein staining of cirrhotic septa. Immunolabeling of biopsy specimens with Vn and tenascin, a marker of ongoing remodeling or recently formed fibrous tissue, could be diagnostically helpful.
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PMID:Vitronectin in the cirrhotic liver: an immunomarker of mature fibrosis. 1177 69