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Query: UMLS:C0239946 (liver fibrosis)
 8,268 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The cellular localization of expression of various genes activated during the course of liver fibrosis and regeneration was studied by immunohistology and in situ hybridization in rat and human liver tissues. Mesenchymal cells proved to be the principal sources of extracellular matrix proteins and of fibrogenic growth factors, whereas the collagenase-activating protease transin/stromelysin gene was transcribed in parenchymal cells as well. Fibrogenesis by the mesenchymal compartment appears to be balanced by fibrolysis controlled by parenchymal cell functions. Continuous parenchymal damage may thus disrupt this balance between fibrogenesis and fibrolysis, resulting in fibrosis.
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PMID:[Pathomorphology of acute and chronic stages of CCl4-induced liver fibrosis: immunohistochemical and in situ hybridization studies]. 144 12

Schistosomal egg granulomas spontaneously secrete fibrogenic factors, suggesting that there exists a molecular link between granulomatous inflammation and hepatic fibrosis in schistosomiasis. To further assess this possibility, we compared elaboration of fibrogenic factors by egg granulomas isolated from Schistosoma mansoni-infected euthymic mice that develop substantial liver fibrosis, with those elaborated by similarly infected congenitally athymic mice that develop minimal fibrosis. Conditioned medium from cultures of granulomas from euthymic mice stimulated fibroblast proliferation, chemotaxis, and synthesis of collagen, collagenase, tissue inhibitor of metalloproteinases, and hyaluronate, whereas those prepared from cultures of granulomas isolated from athymic mice were relatively or absolutely deficient in such activities. These observations provide a correlation between the presence of fibrosis in vivo and the production of fibrogenic factors and reinforce our hypothesis that granuloma-derived fibrogenic factors play a role in the pathogenesis of liver fibrosis in schistosomiasis. Furthermore, the results of this study suggest a central role of T lymphocytes in the fibrogenic process.
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PMID:Fibroblast stimulation in schistosomiasis. IX. Schistosomal egg granulomas from congenitally athymic mice are deficient in production of fibrogenic factors. 215 67

Previous experiments showed that the presence of high levels of acute phase reactants (APR) enhance CCl4-induced liver fibrosis in the rat. A high correlation was found between the degree of fibrosis and alpha 2-macroglobulin of the rat (alpha 2-macrofetoprotein, alpha M-FP) used for monitoring the acute phase response. This acute phase reaction was provoked by epinephrine just before CCl4 treatment was started. In the present study we analyzed the effect of APR by repeating these experiments and estimating liver neutral collagenase with a synthetic substrate and endogenous collagen as a substrate, and liver prolyl-4-hydroxylase. A strong depression of liver collagenase activity was found in rats with a preceding acute phase reaction contrary to the rats that underwent CCl4 treatment only. A high level of alpha M-FP correlated negatively with collagenase activity. Also in vitro alpha M-FP proved to inhibit collagenase activity. Prolyl-4-hydroxylase was increased in the rats during acute phase reaction and correlated highly and positively with alpha M-FP, haptoglobin, and ceruloplasmin. Thus high levels of APR promote development of CCl4-induced fibrosis, partly by anticollagenase activity and partly because of enhancement of prolyl-4-hydroxylase activity. The latter phenomenon can also be explained by the presence of APR, but this has to be proved.
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PMID:Mechanisms by which acute phase proteins enhance development of liver fibrosis: effects on collagenase and prolyl-4-hydroxylase activity in the rat liver. 242 60

Intratracheal application of Bleomycin (Bleo) in rats induces interstitial pneumonitis followed by progressive fibrosis. As the presence of high levels of acute-phase proteins (= reactants = APR), especially alpha 2-macroglobulin of the rat (alpha 2M), enhances liver fibrosis, we investigated whether this phenomenon also occurs in rats with Bleo-induced lung fibrosis. The experiments showed that this is the case; lung fibrosis assessed by measuring hydroxyproline, hexosamine, and prolyl-4-hydroxylase was enhanced when just before Bleo application an acute-phase reaction was induced. This effect can be explained by the inhibitory effect of alpha 2M on collagenase. The experiments showed a significant positive correlation between alpha 2M and parameters of fibrosis. This is especially the case in the third week after Bleo application. Bleo itself does not induce a strong acute-phase reaction, notwithstanding the pneumonitis during the first weeks. The increased fibrosis is accompanied by progressive ventilatory disturbances demonstrated by high arterial pCO2 and low pO2. In patients undergoing Bleo treatment, varying levels of APR can be expected, and this could explain the rapid development of fibrosis in individual cases.
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PMID:Relation between acute-phase proteins and enhanced bleomycin-induced pulmonary fibrosis in the rat. 246 73

The activities of enzymes collagen peptidase (CP), monoaminoxidase (MAO) and N-acetyl-beta-D-glucosaminidase (beta-NAG) in the serum are related to the development of hepatic fibrosis. These enzymes were determined in the sera of 121 liver-biopsied patients who were subdivided by morphological criteria into 4 different grades of fibrosis (0 to greater than or equal to 3). CP shows the best correlation with the extent of fibrosis. beta-NAG, indeed, bears of relationship to the morphologically proven extent of fibrosis, however, significant increases in activity are also encountered in patients with liver diseases, but without liver fibrosis. The validity of these fibrosis markers is calculated in order to differentiate between low- and high-grade fibrosis. With a sensitivity of 86% and a specificity of 92%, CP possesses the best predictive value of 85.7%. The results can still be improved by the combination of CP and beta-NAG.
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PMID:Enzyme activities of collagen peptidase (CP), monoaminoxidase (MAO) and N-acetyl-beta-D-glucosaminidase (beta-NAG) as fibrosis marker in chronic liver diseases. 283 53

Schistosomiasis mansoni is characterized by granulomatous inflammations, deposition of collagen, and irreversible liver fibrosis. In chronic infections fibrosis is cumulative, while collagen synthesis and degradation are diminished. In the present study, we compared collagenase, elastase, and nonspecific neutral protease (NP) activities in isolated vigorous (8-week infection) and immunomodulated (18-20-week infection) liver granulomas. Enzyme activity was localized in the adherent macrophage (greater than 90% purity) and nonadherent eosinophil-rich (greater than 70% purity) cell fractions of the disaggregated granulomas. Collagenase levels were approximately two times higher in granuloma extracts and explant culture supernates of the vigorous as compared with the immunoregulated lesions. However, macrophages and eosinophil-rich cells derived from either type of granuloma secreted similar enzyme levels. Elastase and NP levels in granuloma extracts and secretions of adherent macrophage and eosinophil-rich cell populations were the same in vigorous or immunomodulated lesions but were significantly greater in vigorous granuloma culture supernates. In addition to active collagenase, trypsin activatable latent collagenase was also present in both types of granuloma extracts, explants and eosinophil-rich cell culture supernates. Latent elastase was also detected in granuloma extracts or explant supernates but was absent from secretions of granuloma cells. These results suggest that the presence of active neutral proteases within granulomas may play an important role in the regulation of tissue repair and remodeling during the fibrotic process.
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PMID:Collagenase, elastase, and nonspecific protease production by vigorous or immunomodulated liver granulomas and granuloma macrophages/eosinophils of S mansoni-infected mice. 299 60

Sake, a rice wine, induced hepatic collagen accumulation in rats. This was noted after 16 weeks of a liquid diet containing 35% ethanol by caloric content. However, under similar experimental conditions, whiskey and ethanol did not produce any changes. Hepatic collagenase activities in sake-fed rats were slightly, but significantly, higher than in the whiskey group. The central and pericellular liver fibrosis in sake-fed rats was caused possibly by either accelerated collagen synthesis or maturation, exceeding the increased collagen degradation. Mechanisms of enhanced fibrogenesis in sake-fed rats were discussed.
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PMID:Accumulation of hepatic collagen following long-term administration of sake to rats. 300 74

Liver fibrosis in rats was induced by repeated subcutaneous injections of carbon tetrachloride. Total collagen, soluble and insoluble collagen fractions as well as type I and type III collagen content in the liver were subsequently measured over a 3-18 week period. Liver collagen was found to increase exponentially during this time. Insoluble collagen accumulated more rapidly than soluble forms, and the accumulation of type III collagen was relatively greater than type I collagen. Changes in specific liver enzymes were also observed. Collagenase, collagenolytic cathepsin and collagen peptidase activities all increased. Levels of collagen-degrading enzymes increased rapidly during the first weeks of fibrosis-induction, and were followed by a more gradual increase during the remainder of the study.
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PMID:Dynamics of collagen accumulation and activity of collagen-degrading enzymes in the liver of rats with carbon tetrachloride-induced hepatic fibrosis. 303 9

The interaction between fat-storing cells (FSCs) and Kupffer cells (KCs) in vitro has been studied in an attempt to clarify certain aspects of the pathogenesis of fibrotic process in the liver. FSCs and KCs were isolated from the livers of rats either treated with CCl4 for 6 weeks, or with vitamin A for 6 weeks or from untreated rats by the pronase-collagenase digestion method. FSCs were further purified by centrifugation over a double layered metrizamide gradient, and KCs were separated from other sinusoidal cells by the dish adherence technique. FSCs from CCl4-treated rats divided rapidly, while those from vitamin A-treated rats divided slowly, as compared with untreated rats. Furthermore, the proliferation of FSCs was enhanced in the presence of KCs from CCl4-treated rats, but was slightly suppressed by KCs from normal and vitamin A-treated rats. This enhancement was mediated by a non-dialyzable, soluble factor present in the conditioned medium of KCs from CCl4-treated rats, but was not detected in the conditioned medium of KCs from normal or vitamin A-treated rats. From the present study, a growth factor secreted by KCs from CCl4-treated rats may play an important role in controlling the proliferation of FSCs during the pathogenesis of liver fibrosis.
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PMID:Kupffer cells from CCl4-induced fibrotic livers stimulate proliferation of fat-storing cells. 355 40

Cells with electron-microscopic characteristics of myofibroblasts were isolated from baboon liver biopsy specimens by collagenase digestion and Percoll density gradient centrifugation and then cultured. The cultures consisted of only one cell type. By immunofluorescence, these cells synthesized collagen types I, III, and IV and laminin. Typical features of myofibroblasts were maintained throughout many passages in the culture. To study the effects of ethanol (and its oxidation product acetaldehyde and associated metabolite lactate) on myofibroblast collagen synthesis, the cell cultures were incubated for 24 h in a medium containing either 50 mM ethanol, 200 microM acetaldehyde, or 5 mM lactate. The cells did not contain significant alcohol dehydrogenase activity. Acetaldehyde stimulated significantly (p less than 0.05) myofibroblast collagen synthesis without changing noncollagen protein synthesis or proline pools. Lactate caused a significant (p less than 0.02) increase in intracellular proline pool and collagen synthesis. Ethanol itself did not have any effect on collagen synthesis of myofibroblasts. The stimulation of collagen synthesis of hepatic myofibroblasts by acetaldehyde and lactate may contribute to the development of alcoholic liver fibrosis, as alcohol intake is known to elevate acetaldehyde and lactate in tissues and blood.
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PMID:Acetaldehyde and lactate stimulate collagen synthesis of cultured baboon liver myofibroblasts. 638 Dec 14


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